Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
Identifieur interne : 000420 ( Pmc/Curation ); précédent : 000419; suivant : 000421Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells
Auteurs : Yuanyuan Zhou ; Po-Yee Chung ; Jessica Yuen-Wuen Ma ; Alfred King-Yin Lam ; Simon Law ; Kwok-Wah Chan ; Albert Sun-Chi Chan ; Xingshu Li ; Kim-Hung Lam ; Chung-Hin Chui ; Johnny Cheuk-On TangSource :
- Biology [ 2079-7737 ] ; 2019.
Abstract
Multidrug resistance (MDR) is one of conventional cancer chemotherapy’s limitations. Our group previously synthesized a series of quinoline-based compounds in an attempt to identify novel anticancer agents. With a molecular docking analysis, the novel compound 160a was predicted to target p-glycoprotein, an MDR candidate. The purpose of this study is to evaluate 160a’s MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a’s inhibitory effect, we used a series of parental cancer cell lines (A549, LCC6, KYSE150, and MCF-7), the corresponding doxorubicin-resistant cell lines, an MTS cytotoxicity assay, an intracellular doxorubicin accumulation test, and multidrug resistance assays. The Compusyn program confirmed, with a combination index (CI) value greater than 1, that 160a combined with doxorubicin exerts a synergistic effect. Intracellular doxorubicin accumulation and transported calcein acetoxymethyl (AM) (a substrate for p-glycoprotein) were both increased when cancer cells with MDR were treated with compound 160a. We also showed that compound 160a’s MDR reversal effect can persist for at least 1 h. Taken together, these results suggest that the quinoline compound 160a possesses high potential to reverse MDR by inhibiting p-glycoprotein-mediated drug efflux in cancer cells with MDR.
Url:
DOI: 10.3390/biology8040075
PubMed: 31581572
PubMed Central: 6955663
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<front><div type="abstract" xml:lang="en"><p>Multidrug resistance (MDR) is one of conventional cancer chemotherapy’s limitations. Our group previously synthesized a series of quinoline-based compounds in an attempt to identify novel anticancer agents. With a molecular docking analysis, the novel compound 160a was predicted to target p-glycoprotein, an MDR candidate. The purpose of this study is to evaluate 160a’s MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a’s inhibitory effect, we used a series of parental cancer cell lines (A549, LCC6, KYSE150, and MCF-7), the corresponding doxorubicin-resistant cell lines, an MTS cytotoxicity assay, an intracellular doxorubicin accumulation test, and multidrug resistance assays. The Compusyn program confirmed, with a combination index (CI) value greater than 1, that 160a combined with doxorubicin exerts a synergistic effect. Intracellular doxorubicin accumulation and transported calcein acetoxymethyl (AM) (a substrate for p-glycoprotein) were both increased when cancer cells with MDR were treated with compound 160a. We also showed that compound 160a’s MDR reversal effect can persist for at least 1 h. Taken together, these results suggest that the quinoline compound 160a possesses high potential to reverse MDR by inhibiting p-glycoprotein-mediated drug efflux in cancer cells with MDR.</p>
</div>
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<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name>
</author>
<author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name>
</author>
<author><name sortKey="Dikshit, R" uniqKey="Dikshit R">R. Dikshit</name>
</author>
<author><name sortKey="Eser, S" uniqKey="Eser S">S. Eser</name>
</author>
<author><name sortKey="Mathers, C" uniqKey="Mathers C">C. Mathers</name>
</author>
<author><name sortKey="Rebelo, M" uniqKey="Rebelo M">M. Rebelo</name>
</author>
<author><name sortKey="Parkin, D M" uniqKey="Parkin D">D.M. Parkin</name>
</author>
<author><name sortKey="Forman, D" uniqKey="Forman D">D. Forman</name>
</author>
<author><name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Atalay, C" uniqKey="Atalay C">C. Atalay</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ojima, I" uniqKey="Ojima I">I. Ojima</name>
</author>
<author><name sortKey="Bounaud, P Y" uniqKey="Bounaud P">P.Y. Bounaud</name>
</author>
<author><name sortKey="Oderda, C F" uniqKey="Oderda C">C.F. Oderda</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wu, Q" uniqKey="Wu Q">Q. Wu</name>
</author>
<author><name sortKey="Yang, Z P" uniqKey="Yang Z">Z.P. Yang</name>
</author>
<author><name sortKey="Nie, Y Z" uniqKey="Nie Y">Y.Z. Nie</name>
</author>
<author><name sortKey="Shi, Y Q" uniqKey="Shi Y">Y.Q. Shi</name>
</author>
<author><name sortKey="Fan, D M" uniqKey="Fan D">D.M. Fan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sharom, F J" uniqKey="Sharom F">F.J. Sharom</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stewart, A" uniqKey="Stewart A">A. Stewart</name>
</author>
<author><name sortKey="Steiner, J" uniqKey="Steiner J">J. Steiner</name>
</author>
<author><name sortKey="Mellows, G" uniqKey="Mellows G">G. Mellows</name>
</author>
<author><name sortKey="Laguda, B" uniqKey="Laguda B">B. Laguda</name>
</author>
<author><name sortKey="Norris, D" uniqKey="Norris D">D. Norris</name>
</author>
<author><name sortKey="Bevan, P" uniqKey="Bevan P">P. Bevan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patil, Y B" uniqKey="Patil Y">Y.B. Patil</name>
</author>
<author><name sortKey="Swaminathan, S K" uniqKey="Swaminathan S">S.K. Swaminathan</name>
</author>
<author><name sortKey="Sadhukha, T" uniqKey="Sadhukha T">T. Sadhukha</name>
</author>
<author><name sortKey="Ma, L A" uniqKey="Ma L">L.A. Ma</name>
</author>
<author><name sortKey="Panyam, J" uniqKey="Panyam J">J. Panyam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fardel, O" uniqKey="Fardel O">O. Fardel</name>
</author>
<author><name sortKey="Lecureur, V" uniqKey="Lecureur V">V. Lecureur</name>
</author>
<author><name sortKey="Guillouzo, A" uniqKey="Guillouzo A">A. Guillouzo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liang, Y" uniqKey="Liang Y">Y. Liang</name>
</author>
<author><name sortKey="Zhou, Y Y" uniqKey="Zhou Y">Y.Y. Zhou</name>
</author>
<author><name sortKey="Zhang, J W" uniqKey="Zhang J">J.W. Zhang</name>
</author>
<author><name sortKey="Liu, Y N" uniqKey="Liu Y">Y.N. Liu</name>
</author>
<author><name sortKey="Guan, T Y" uniqKey="Guan T">T.Y. Guan</name>
</author>
<author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name>
</author>
<author><name sortKey="Xing, L" uniqKey="Xing L">L. Xing</name>
</author>
<author><name sortKey="Rao, T" uniqKey="Rao T">T. Rao</name>
</author>
<author><name sortKey="Zhou, L J" uniqKey="Zhou L">L.J. Zhou</name>
</author>
<author><name sortKey="Hao, K" uniqKey="Hao K">K. Hao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kapse Mistry, S" uniqKey="Kapse Mistry S">S. Kapse-Mistry</name>
</author>
<author><name sortKey="Govender, T" uniqKey="Govender T">T. Govender</name>
</author>
<author><name sortKey="Srivastava, R" uniqKey="Srivastava R">R. Srivastava</name>
</author>
<author><name sortKey="Yergeri, M" uniqKey="Yergeri M">M. Yergeri</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dantzig, A H" uniqKey="Dantzig A">A.H. Dantzig</name>
</author>
<author><name sortKey="De Alwis, D P" uniqKey="De Alwis D">D.P. de Alwis</name>
</author>
<author><name sortKey="Burgess, M" uniqKey="Burgess M">M. Burgess</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thomas, H" uniqKey="Thomas H">H. Thomas</name>
</author>
<author><name sortKey="Coley, H M" uniqKey="Coley H">H.M. Coley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ozben, T" uniqKey="Ozben T">T. Ozben</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Foote, S J" uniqKey="Foote S">S.J. Foote</name>
</author>
<author><name sortKey="Kyle, D E" uniqKey="Kyle D">D.E. Kyle</name>
</author>
<author><name sortKey="Martin, R K" uniqKey="Martin R">R.K. Martin</name>
</author>
<author><name sortKey="Oduola, A M J" uniqKey="Oduola A">A.M.J. Oduola</name>
</author>
<author><name sortKey="Forsyth, K" uniqKey="Forsyth K">K. Forsyth</name>
</author>
<author><name sortKey="Kemp, D J" uniqKey="Kemp D">D.J. Kemp</name>
</author>
<author><name sortKey="Cowman, A F" uniqKey="Cowman A">A.F. Cowman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leonessa, F" uniqKey="Leonessa F">F. Leonessa</name>
</author>
<author><name sortKey="Green, D" uniqKey="Green D">D. Green</name>
</author>
<author><name sortKey="Licht, T" uniqKey="Licht T">T. Licht</name>
</author>
<author><name sortKey="Wright, A" uniqKey="Wright A">A. Wright</name>
</author>
<author><name sortKey="Wingatelegette, K" uniqKey="Wingatelegette K">K. WingateLegette</name>
</author>
<author><name sortKey="Lippman, J" uniqKey="Lippman J">J. Lippman</name>
</author>
<author><name sortKey="Gottesman, M M" uniqKey="Gottesman M">M.M. Gottesman</name>
</author>
<author><name sortKey="Clarke, R" uniqKey="Clarke R">R. Clarke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tang, J C" uniqKey="Tang J">J.C. Tang</name>
</author>
<author><name sortKey="Wan, T S" uniqKey="Wan T">T.S. Wan</name>
</author>
<author><name sortKey="Wong, N" uniqKey="Wong N">N. Wong</name>
</author>
<author><name sortKey="Pang, E" uniqKey="Pang E">E. Pang</name>
</author>
<author><name sortKey="Lam, K Y" uniqKey="Lam K">K.Y. Lam</name>
</author>
<author><name sortKey="Law, S Y" uniqKey="Law S">S.Y. Law</name>
</author>
<author><name sortKey="Chow, L M" uniqKey="Chow L">L.M. Chow</name>
</author>
<author><name sortKey="Ma, E S" uniqKey="Ma E">E.S. Ma</name>
</author>
<author><name sortKey="Chan, L C" uniqKey="Chan L">L.C. Chan</name>
</author>
<author><name sortKey="Wong, J" uniqKey="Wong J">J. Wong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name>
</author>
<author><name sortKey="Jin, Y S" uniqKey="Jin Y">Y.S. Jin</name>
</author>
<author><name sortKey="Chen, X H" uniqKey="Chen X">X.H. Chen</name>
</author>
<author><name sortKey="Jin, C" uniqKey="Jin C">C. Jin</name>
</author>
<author><name sortKey="Law, S" uniqKey="Law S">S. Law</name>
</author>
<author><name sortKey="Tsao, S W" uniqKey="Tsao S">S.W. Tsao</name>
</author>
<author><name sortKey="Kwong, Y L" uniqKey="Kwong Y">Y.L. Kwong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roundhill, E A" uniqKey="Roundhill E">E.A. Roundhill</name>
</author>
<author><name sortKey="Jabri, S" uniqKey="Jabri S">S. Jabri</name>
</author>
<author><name sortKey="Burchill, S A" uniqKey="Burchill S">S.A. Burchill</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lynn, D E" uniqKey="Lynn D">D.E. Lynn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Keiser, M J" uniqKey="Keiser M">M.J. Keiser</name>
</author>
<author><name sortKey="Roth, B L" uniqKey="Roth B">B.L. Roth</name>
</author>
<author><name sortKey="Armbruster, B N" uniqKey="Armbruster B">B.N. Armbruster</name>
</author>
<author><name sortKey="Ernsberger, P" uniqKey="Ernsberger P">P. Ernsberger</name>
</author>
<author><name sortKey="Irwin, J J" uniqKey="Irwin J">J.J. Irwin</name>
</author>
<author><name sortKey="Shoichet, B K" uniqKey="Shoichet B">B.K. Shoichet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barltrop, J A" uniqKey="Barltrop J">J.A. Barltrop</name>
</author>
<author><name sortKey="Owen, T C" uniqKey="Owen T">T.C. Owen</name>
</author>
<author><name sortKey="Cory, A H" uniqKey="Cory A">A.H. Cory</name>
</author>
<author><name sortKey="Cory, J G" uniqKey="Cory J">J.G. Cory</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Riss, T L" uniqKey="Riss T">T.L. Riss</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qiu, Q Q" uniqKey="Qiu Q">Q.Q. Qiu</name>
</author>
<author><name sortKey="Liu, B M" uniqKey="Liu B">B.M. Liu</name>
</author>
<author><name sortKey="Cui, J" uniqKey="Cui J">J. Cui</name>
</author>
<author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name>
</author>
<author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name>
</author>
<author><name sortKey="Qiang, H" uniqKey="Qiang H">H. Qiang</name>
</author>
<author><name sortKey="Li, J M" uniqKey="Li J">J.M. Li</name>
</author>
<author><name sortKey="Liao, C" uniqKey="Liao C">C. Liao</name>
</author>
<author><name sortKey="Zhang, B" uniqKey="Zhang B">B. Zhang</name>
</author>
<author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, N" uniqKey="Zhang N">N. Zhang</name>
</author>
<author><name sortKey="Fu, J N" uniqKey="Fu J">J.N. Fu</name>
</author>
<author><name sortKey="Chou, T C" uniqKey="Chou T">T.C. Chou</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chou, T C" uniqKey="Chou T">T.C. Chou</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qiu, X S" uniqKey="Qiu X">X.S. Qiu</name>
</author>
<author><name sortKey="Tang, N L S" uniqKey="Tang N">N.L.S. Tang</name>
</author>
<author><name sortKey="Yeung, H Y" uniqKey="Yeung H">H.Y. Yeung</name>
</author>
<author><name sortKey="Cheng, J C Y" uniqKey="Cheng J">J.C.Y. Cheng</name>
</author>
<author><name sortKey="Qiu, Y" uniqKey="Qiu Y">Y. Qiu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Honda, M" uniqKey="Honda M">M. Honda</name>
</author>
<author><name sortKey="Miura, A" uniqKey="Miura A">A. Miura</name>
</author>
<author><name sortKey="Izumi, Y" uniqKey="Izumi Y">Y. Izumi</name>
</author>
<author><name sortKey="Kato, T" uniqKey="Kato T">T. Kato</name>
</author>
<author><name sortKey="Ryotokuji, T" uniqKey="Ryotokuji T">T. Ryotokuji</name>
</author>
<author><name sortKey="Monma, K" uniqKey="Monma K">K. Monma</name>
</author>
<author><name sortKey="Fujiwara, J" uniqKey="Fujiwara J">J. Fujiwara</name>
</author>
<author><name sortKey="Egashira, H" uniqKey="Egashira H">H. Egashira</name>
</author>
<author><name sortKey="Nemoto, T" uniqKey="Nemoto T">T. Nemoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yu, L" uniqKey="Yu L">L. Yu</name>
</author>
<author><name sortKey="Wu, W K" uniqKey="Wu W">W.K. Wu</name>
</author>
<author><name sortKey="Li, Z J" uniqKey="Li Z">Z.J. Li</name>
</author>
<author><name sortKey="Liu, Q C" uniqKey="Liu Q">Q.C. Liu</name>
</author>
<author><name sortKey="Li, H T" uniqKey="Li H">H.T. Li</name>
</author>
<author><name sortKey="Wu, Y C" uniqKey="Wu Y">Y.C. Wu</name>
</author>
<author><name sortKey="Cho, C H" uniqKey="Cho C">C.H. Cho</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mechetner, E" uniqKey="Mechetner E">E. Mechetner</name>
</author>
<author><name sortKey="Kyshtoobayeva, A" uniqKey="Kyshtoobayeva A">A. Kyshtoobayeva</name>
</author>
<author><name sortKey="Zonis, S" uniqKey="Zonis S">S. Zonis</name>
</author>
<author><name sortKey="Kim, H" uniqKey="Kim H">H. Kim</name>
</author>
<author><name sortKey="Stroup, R" uniqKey="Stroup R">R. Stroup</name>
</author>
<author><name sortKey="Garcia, R" uniqKey="Garcia R">R. Garcia</name>
</author>
<author><name sortKey="Parker, R J" uniqKey="Parker R">R.J. Parker</name>
</author>
<author><name sortKey="Fruehauf, J P" uniqKey="Fruehauf J">J.P. Fruehauf</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berridge, M V" uniqKey="Berridge M">M.V. Berridge</name>
</author>
<author><name sortKey="Tan, A S" uniqKey="Tan A">A.S. Tan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Omidi, M" uniqKey="Omidi M">M. Omidi</name>
</author>
<author><name sortKey="Fatehinya, A" uniqKey="Fatehinya A">A. Fatehinya</name>
</author>
<author><name sortKey="Farahani, M" uniqKey="Farahani M">M. Farahani</name>
</author>
<author><name sortKey="Akbari, Z" uniqKey="Akbari Z">Z. Akbari</name>
</author>
<author><name sortKey="Shahmoradi, S" uniqKey="Shahmoradi S">S. Shahmoradi</name>
</author>
<author><name sortKey="Yazdian, F" uniqKey="Yazdian F">F. Yazdian</name>
</author>
<author><name sortKey="Tahriri, M" uniqKey="Tahriri M">M. Tahriri</name>
</author>
<author><name sortKey="Moharamzadeh, K" uniqKey="Moharamzadeh K">K. Moharamzadeh</name>
</author>
<author><name sortKey="Tayebi, L" uniqKey="Tayebi L">L. Tayebi</name>
</author>
<author><name sortKey="Vashaee, D" uniqKey="Vashaee D">D. Vashaee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meng, J R" uniqKey="Meng J">J.R. Meng</name>
</author>
<author><name sortKey="Dai, B B" uniqKey="Dai B">B.B. Dai</name>
</author>
<author><name sortKey="Fang, B L" uniqKey="Fang B">B.L. Fang</name>
</author>
<author><name sortKey="Bekele, B N" uniqKey="Bekele B">B.N. Bekele</name>
</author>
<author><name sortKey="Bornmann, W G" uniqKey="Bornmann W">W.G. Bornmann</name>
</author>
<author><name sortKey="Sun, D L" uniqKey="Sun D">D.L. Sun</name>
</author>
<author><name sortKey="Peng, Z H" uniqKey="Peng Z">Z.H. Peng</name>
</author>
<author><name sortKey="Herbst, R S" uniqKey="Herbst R">R.S. Herbst</name>
</author>
<author><name sortKey="Papadimitrakopoulou, V" uniqKey="Papadimitrakopoulou V">V. Papadimitrakopoulou</name>
</author>
<author><name sortKey="Minna, J D" uniqKey="Minna J">J.D. Minna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pasquier, E" uniqKey="Pasquier E">E. Pasquier</name>
</author>
<author><name sortKey="Ciccolini, J" uniqKey="Ciccolini J">J. Ciccolini</name>
</author>
<author><name sortKey="Carre, M" uniqKey="Carre M">M. Carre</name>
</author>
<author><name sortKey="Giacometti, S" uniqKey="Giacometti S">S. Giacometti</name>
</author>
<author><name sortKey="Fanciullino, R" uniqKey="Fanciullino R">R. Fanciullino</name>
</author>
<author><name sortKey="Pouchy, C" uniqKey="Pouchy C">C. Pouchy</name>
</author>
<author><name sortKey="Montero, M P" uniqKey="Montero M">M.P. Montero</name>
</author>
<author><name sortKey="Serdjebi, C" uniqKey="Serdjebi C">C. Serdjebi</name>
</author>
<author><name sortKey="Kavallaris, M" uniqKey="Kavallaris M">M. Kavallaris</name>
</author>
<author><name sortKey="Andre, N" uniqKey="Andre N">N. Andre</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tiberghien, F" uniqKey="Tiberghien F">F. Tiberghien</name>
</author>
<author><name sortKey="Loor, F" uniqKey="Loor F">F. Loor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aszalos, A" uniqKey="Aszalos A">A. Aszalos</name>
</author>
<author><name sortKey="Thompson, K" uniqKey="Thompson K">K. Thompson</name>
</author>
<author><name sortKey="Yin, J J" uniqKey="Yin J">J.J. Yin</name>
</author>
<author><name sortKey="Ross, D D" uniqKey="Ross D">D.D. Ross</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mistry, P" uniqKey="Mistry P">P. Mistry</name>
</author>
<author><name sortKey="Stewart, A J" uniqKey="Stewart A">A.J. Stewart</name>
</author>
<author><name sortKey="Dangerfield, W" uniqKey="Dangerfield W">W. Dangerfield</name>
</author>
<author><name sortKey="Okiji, S" uniqKey="Okiji S">S. Okiji</name>
</author>
<author><name sortKey="Liddle, C" uniqKey="Liddle C">C. Liddle</name>
</author>
<author><name sortKey="Bootle, D" uniqKey="Bootle D">D. Bootle</name>
</author>
<author><name sortKey="Plumb, J A" uniqKey="Plumb J">J.A. Plumb</name>
</author>
<author><name sortKey="Templeton, D" uniqKey="Templeton D">D. Templeton</name>
</author>
<author><name sortKey="Charlton, P" uniqKey="Charlton P">P. Charlton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Vahedi, S" uniqKey="Vahedi S">S. Vahedi</name>
</author>
<author><name sortKey="Lusvarghi, S" uniqKey="Lusvarghi S">S. Lusvarghi</name>
</author>
<author><name sortKey="Pluchino, K" uniqKey="Pluchino K">K. Pluchino</name>
</author>
<author><name sortKey="Shafrir, Y" uniqKey="Shafrir Y">Y. Shafrir</name>
</author>
<author><name sortKey="Durell, S R" uniqKey="Durell S">S.R. Durell</name>
</author>
<author><name sortKey="Gottesman, M M" uniqKey="Gottesman M">M.M. Gottesman</name>
</author>
<author><name sortKey="Ambudkar, S V" uniqKey="Ambudkar S">S.V. Ambudkar</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Seebacher, N A" uniqKey="Seebacher N">N.A. Seebacher</name>
</author>
<author><name sortKey="Richardson, D R" uniqKey="Richardson D">D.R. Richardson</name>
</author>
<author><name sortKey="Jansson, P J" uniqKey="Jansson P">P.J. Jansson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thummel, K E" uniqKey="Thummel K">K.E. Thummel</name>
</author>
<author><name sortKey="Wilkinson, G R" uniqKey="Wilkinson G">G.R. Wilkinson</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biology (Basel)</journal-id>
<journal-id journal-id-type="iso-abbrev">Biology (Basel)</journal-id>
<journal-id journal-id-type="publisher-id">biology</journal-id>
<journal-title-group><journal-title>Biology</journal-title>
</journal-title-group>
<issn pub-type="epub">2079-7737</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31581572</article-id>
<article-id pub-id-type="pmc">6955663</article-id>
<article-id pub-id-type="doi">10.3390/biology8040075</article-id>
<article-id pub-id-type="publisher-id">biology-08-00075</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Development of a Novel Quinoline Derivative as a P-Glycoprotein Inhibitor to Reverse Multidrug Resistance in Cancer Cells</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-3684-6126</contrib-id>
<name><surname>Zhou</surname>
<given-names>Yuanyuan</given-names>
</name>
<xref ref-type="aff" rid="af1-biology-08-00075">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-4461-1343</contrib-id>
<name><surname>Chung</surname>
<given-names>Po-yee</given-names>
</name>
<xref ref-type="aff" rid="af1-biology-08-00075">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Jessica Yuen-wuen</given-names>
</name>
<xref ref-type="aff" rid="af2-biology-08-00075">2</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-2771-564X</contrib-id>
<name><surname>Lam</surname>
<given-names>Alfred King-yin</given-names>
</name>
<xref ref-type="aff" rid="af3-biology-08-00075">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Law</surname>
<given-names>Simon</given-names>
</name>
<xref ref-type="aff" rid="af4-biology-08-00075">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>Kwok-wah</given-names>
</name>
<xref ref-type="aff" rid="af5-biology-08-00075">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>Albert Sun-chi</given-names>
</name>
<xref ref-type="aff" rid="af6-biology-08-00075">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Xingshu</given-names>
</name>
<xref ref-type="aff" rid="af6-biology-08-00075">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lam</surname>
<given-names>Kim-hung</given-names>
</name>
<xref ref-type="aff" rid="af1-biology-08-00075">1</xref>
<xref rid="c1-biology-08-00075" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chui</surname>
<given-names>Chung-hin</given-names>
</name>
<xref ref-type="aff" rid="af1-biology-08-00075">1</xref>
<xref rid="c1-biology-08-00075" ref-type="corresp">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tang</surname>
<given-names>Johnny Cheuk-on</given-names>
</name>
<xref ref-type="aff" rid="af1-biology-08-00075">1</xref>
<xref rid="c1-biology-08-00075" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-biology-08-00075"><label>1</label>
State Key Laboratory of Chemical Biology and Drug Discovery, Lo Ka Chung Centre for Natural Anticancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong 999077, China;<email>yuanyuan.09.zhou@connect.polyu.hk</email>
(Y.Z.);</aff>
<aff id="af2-biology-08-00075"><label>2</label>
School of Optometry, The Hong Kong Polytechnic University, Hong Kong 999077, China;<email>majessicayuenwuen@gmail.com</email>
</aff>
<aff id="af3-biology-08-00075"><label>3</label>
Griffith Medical School, Griffith University, Gold Coast, QLD 4222, Australia;<email>A.Lam@griffith.edu.au</email>
</aff>
<aff id="af4-biology-08-00075"><label>4</label>
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>slaw@hku.hk</email>
</aff>
<aff id="af5-biology-08-00075"><label>5</label>
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;<email>kwchan@pathology.hku.hk</email>
</aff>
<aff id="af6-biology-08-00075"><label>6</label>
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;<email>chenxz3@mail.sysu.edu.cn</email>
(A.S.-c.C.);<email>lixsh@mail.sysu.edu.cn</email>
(X.L.)</aff>
<author-notes><corresp id="c1-biology-08-00075"><label>*</label>
Correspondence: <email>kim.hung.lam@polyu.edu.hk</email>
(K.-h.L.); <email>chui.ch@gmail.com</email>
(C.-h.C.); <email>jcotang2@outlook.com</email>
(J.C.-o.T.); Tel.: +852-3400-8705 (K.-h.L.); +852-3400-8748 (C.-h.C.); +852-3400-8727 (J.C.-o.T.); Fax: +852-3013-8935 (K.-h.L.); +852-3013-8935 (C.-h.C.); +852-3013-8935 (J.C.-o.T.)</corresp>
</author-notes>
<pub-date pub-type="epub"><day>01</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>12</month>
<year>2019</year>
</pub-date>
<volume>8</volume>
<issue>4</issue>
<elocation-id>75</elocation-id>
<history><date date-type="received"><day>06</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>27</day>
<month>9</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Multidrug resistance (MDR) is one of conventional cancer chemotherapy’s limitations. Our group previously synthesized a series of quinoline-based compounds in an attempt to identify novel anticancer agents. With a molecular docking analysis, the novel compound 160a was predicted to target p-glycoprotein, an MDR candidate. The purpose of this study is to evaluate 160a’s MDR reversal effect and investigate the underlying mechanism at the molecular level. To investigate 160a’s inhibitory effect, we used a series of parental cancer cell lines (A549, LCC6, KYSE150, and MCF-7), the corresponding doxorubicin-resistant cell lines, an MTS cytotoxicity assay, an intracellular doxorubicin accumulation test, and multidrug resistance assays. The Compusyn program confirmed, with a combination index (CI) value greater than 1, that 160a combined with doxorubicin exerts a synergistic effect. Intracellular doxorubicin accumulation and transported calcein acetoxymethyl (AM) (a substrate for p-glycoprotein) were both increased when cancer cells with MDR were treated with compound 160a. We also showed that compound 160a’s MDR reversal effect can persist for at least 1 h. Taken together, these results suggest that the quinoline compound 160a possesses high potential to reverse MDR by inhibiting p-glycoprotein-mediated drug efflux in cancer cells with MDR.</p>
</abstract>
<kwd-group><kwd>anticancer</kwd>
<kwd>multidrug resistance</kwd>
<kwd>p-glycoprotein</kwd>
<kwd>quinoline compounds</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="biology-08-00075-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>The structure of compound 160a.</p>
</caption>
<graphic xlink:href="biology-08-00075-g001"></graphic>
</fig>
<fig id="biology-08-00075-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Cytotoxic effect of different concentrations of doxorubicin on parental and doxorubicin-resistant cancer cells co-cultured with compound 160a. (<bold>a</bold>
) The relative MTS value of doxorubicin in the parental and dox-resistant A549 cell lines; (<bold>b</bold>
) the relative MTS value of doxorubicin combined with compound 160a (5 µg/mL, 10 µg/mL) in the dox-resistant A549 cell lines; (<bold>c</bold>
) the relative MTS value of doxorubicin in the parental and dox-resistant KYSE150 cell lines; (<bold>d</bold>
) the relative MTS value of doxorubicin combined with compound 160a (5 µg/mL, 10 µg/mL) in dox-resistant KYSE150 cells; (<bold>e</bold>
) the relative MTS value of compound 160a in NE-3 non-cancer cells; (<bold>f</bold>
) the relative MTS value of doxorubicin in NE-3 non-cancer cells. Dissolved in dimethyl sulfoxide (DMSO) (0.1%) was applied as a vehicle control (<italic>n</italic>
= 4). ^ <italic>p</italic>
< 0.05, ^^ <italic>p</italic>
< 0.01 comparing the 5 µg/mL compound 160a group with the control group; * <italic>p</italic>
< 0.05, ** <italic>p</italic>
< 0.01 comparing the 10 µg/mL compound 160a group with the control group.</p>
</caption>
<graphic xlink:href="biology-08-00075-g002"></graphic>
</fig>
<fig id="biology-08-00075-f003" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Analysis of the synergistic effect of compound 160a and doxorubicin on the dox-resistant cancer cell line A549/DOX using the CompuSyn program. (<bold>a</bold>
) Dose–effect curve of compound 160a, doxorubicin, and compound 160a combined with doxorubicin versus relative MTS value; (<bold>b</bold>
) Fa–CI plot (Chou–Talalay Plot). Fa, fraction of system affected; CI, combination index. CI = 1 indicates an additive effect; CI < 1 indicates synergism; CI > 1 indicates antagonism [<xref rid="B25-biology-08-00075" ref-type="bibr">25</xref>
]. <italic>n</italic>
= 3. Cm, combination; Dox, doxorubicin.</p>
</caption>
<graphic xlink:href="biology-08-00075-g003"></graphic>
</fig>
<fig id="biology-08-00075-f004" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>Cell proliferation curves of doxorubicin-resistant cells co-cultured with compound 160a, doxorubicin, and compound 160a combined with doxorubicin. (<bold>a</bold>
) A549/DOX cells; (<bold>b</bold>
) KYSE150/DOX cells; (<bold>c</bold>
) LCC6/MDR cells; (<bold>d</bold>
) MX100 cells. DMSO (0.1%) was applied as a vehicle control. <italic>n</italic>
= 3. * <italic>p</italic>
< 0.05, ** <italic>p</italic>
< 0.01 comparing the doxorubicin combined with compound 160a group with the control group; ^ <italic>p</italic>
< 0.05, ^^ <italic>p</italic>
< 0.01 comparing the doxorubicin combined with compound 160a groups with the doxorubicin alone group.</p>
</caption>
<graphic xlink:href="biology-08-00075-g004"></graphic>
</fig>
<fig id="biology-08-00075-f005" orientation="portrait" position="float"><label>Figure 5</label>
<caption><p>Effects of reversing the MDR phenotype in the doxorubicin-resistant A549 cell line. (<bold>a</bold>
) Calcein acetoxymethyl (AM) retention produced by compound 160a on the doxorubicin-resistant A549 cell line; (<bold>b</bold>
) the intensity of the green fluorescence signal from the calcein AM counted in the filter channel (FL-1) using a flow cytometric analysis of calcein AM with an increasing concentration of compound 160a (2, 10, and 20 μg/mL). DMSO (0.1%) was applied as a vehicle control. Verapamil (50 μg/mL) was applied as a positive control. <italic>n</italic>
= 3. * <italic>p</italic>
< 0.05, comparing with blank control group.</p>
</caption>
<graphic xlink:href="biology-08-00075-g005"></graphic>
</fig>
<fig id="biology-08-00075-f006" orientation="portrait" position="float"><label>Figure 6</label>
<caption><p>Images of fluorescent signals of calcein AM accumulated in doxorubicin (dox)-resistant A549 cells after treatment with different concentrations of compound 160a for 30 min. (<bold>a</bold>
–<bold>c</bold>
): Calcein AM signals of A549 parental cells treated with DMSO; (<bold>d</bold>
–<bold>f</bold>
): Calcein AM signals of dox-resistant A549 cells treated with DMSO; (<bold>g</bold>
–<bold>i</bold>
): Calcein AM signals of dox-resistant A549 cells treated with 5 μg/mL compound 160a; (<bold>j</bold>
–<bold>l</bold>
): Calcein AM signals of dox-resistant A549 cells treated with 25 μg/mL compound 160a; (<bold>m</bold>
–<bold>o</bold>
): Calcein AM signals of dox-resistant A549 cells treated with 50 μg/mL compound 160a; (<bold>p</bold>
–<bold>r</bold>
): Calcein AM signals of dox-resistant A549 cells treated with verapamil. DMSO (0.1%) was applied as a vehicle control; 50 μg/mL verapamil was applied as a positive control.</p>
</caption>
<graphic xlink:href="biology-08-00075-g006a"></graphic>
<graphic xlink:href="biology-08-00075-g006b"></graphic>
</fig>
<fig id="biology-08-00075-f007" orientation="portrait" position="float"><label>Figure 7</label>
<caption><p>Summary of the fluorescence intensity of intracellular calcein AM in the A549 and A549/DOX cell lines treated with compound 160a and observed using a confocal microscope. DMSO (0.1%) was applied as a vehicle control; 50 μg/mL verapamil was applied as a positive control. Fluorescence intensity was measured by Image J.</p>
</caption>
<graphic xlink:href="biology-08-00075-g007"></graphic>
</fig>
<fig id="biology-08-00075-f008" orientation="portrait" position="float"><label>Figure 8</label>
<caption><p>Effect of compound 160a on intracellular DOX accumulation in parental/DOX-resistant cells. (<bold>a</bold>
) Intracellular doxorubicin concentration of LCC6/LCC6 MDR cells treated with compound 160a; (<bold>b</bold>
) Intracellular doxorubicin concentration of KYSE150/KYSE150-DOX cells treated with compound 160a; (<bold>c</bold>
) Intracellular doxorubicin concentration of A549/A549-DOX cells treated with compound 160a; and (<bold>d</bold>
) Intracellular doxorubicin concentration of MCF-7/MX-100 cells treated with compound 160a. DMSO (0.1%) was applied as a negative control; 50 µg/mL verapamil was applied as a positive control. <italic>n</italic>
= 3. * <italic>p</italic>
<inline-formula><mml:math id="mm4"><mml:mrow><mml:mrow><mml:mo><</mml:mo>
</mml:mrow>
</mml:mrow>
</mml:math>
</inline-formula>
0.05, ** <italic>p</italic>
<inline-formula><mml:math id="mm5"><mml:mrow><mml:mrow><mml:mo><</mml:mo>
</mml:mrow>
</mml:mrow>
</mml:math>
</inline-formula>
0.01 comparing the other groups with the dox-resistant control group; ^ <italic>p</italic>
< 0.05, ^^ <italic>p</italic>
< 0.01 comparing the compound-160a-treated groups with the verapamil group.</p>
</caption>
<graphic xlink:href="biology-08-00075-g008"></graphic>
</fig>
<fig id="biology-08-00075-f009" orientation="portrait" position="float"><label>Figure 9</label>
<caption><p>Duration of the MDR reversal effect of compound 160a on doxorubicin in DOX-resistant cancer cells. (<bold>a</bold>
) Duration of the MDR reversal effect of compound 160a on doxorubicin in A549/DOX cancer cells; (<bold>b</bold>
) Duration of the MDR reversal effect of compound 160a on doxorubicin in MX100 cancer cells. DMSO (0.1%) was applied as a vehicle control. Cell viability was determined by an MTS assay. <italic>n</italic>
= 3. * <italic>p</italic>
< 0.05; ** <italic>p</italic>
< 0.01.</p>
</caption>
<graphic xlink:href="biology-08-00075-g009"></graphic>
</fig>
<table-wrap id="biology-08-00075-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">biology-08-00075-t001_Table 1</object-id>
<label>Table 1</label>
<caption><p>Top three predicted human protein targets for compound 160a based on the similarity ensemble approach (SEA).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Rank</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target Key</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target Name</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Description</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic>
-Value</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">MaxTC</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MTR1A_HUMAN+5</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MTNR1A</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Melatonin receptor type 1A</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.272e<sup>−19</sup>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.40</td>
</tr>
<tr><td align="center" valign="middle" rowspan="1" colspan="1">2</td>
<td align="center" valign="middle" rowspan="1" colspan="1">MDR1_HUMAN+5</td>
<td align="center" valign="middle" rowspan="1" colspan="1">ABCB1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Multidrug resistance protein 1</td>
<td align="center" valign="middle" rowspan="1" colspan="1">3.235e<sup>−18</sup>
</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.46</td>
</tr>
<tr><td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">3</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">ROCK2_HUMAN+5</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">ROCK2</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Rho-associated protein kinase 2</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">3.902e<sup>−18</sup>
</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.32</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>MaxTC, maximum target complementary value.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="biology-08-00075-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">biology-08-00075-t002_Table 2</object-id>
<label>Table 2</label>
<caption><p>IC<sub>50</sub>
values (μg/mL) of doxorubicin (Dox), Dox combined with compound 160a on parental cancer cell lines or Dox-resistance cancer cell lines, and Dox or compound 160a alone on non-tumor cell line (NE-3).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="2" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">Cell Lines</th>
<th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">IC<sub>50</sub>
Value (μg/mL)</th>
</tr>
<tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dox</th>
<th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dox + 5μg/mL 160a</th>
<th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dox + 10μg/mL 160a</th>
</tr>
</thead>
<tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Parental A549</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.408</td>
<td align="center" valign="middle" rowspan="1" colspan="1">N.A.</td>
<td align="center" valign="middle" rowspan="1" colspan="1">N.A.</td>
</tr>
<tr><td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dox-resistance A549</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.542</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.182</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.195</td>
</tr>
<tr><td align="center" valign="middle" rowspan="1" colspan="1">Parental KYSE150</td>
<td align="center" valign="middle" rowspan="1" colspan="1">0.475</td>
<td align="center" valign="middle" rowspan="1" colspan="1">N.A.</td>
<td align="center" valign="middle" rowspan="1" colspan="1">N.A.</td>
</tr>
<tr><td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dox-resistance KYSE150</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.735</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.164</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.057</td>
</tr>
<tr><td align="center" valign="middle" rowspan="1" colspan="1"></td>
<td align="center" valign="middle" rowspan="1" colspan="1"><bold>Dox</bold>
</td>
<td colspan="2" align="center" valign="middle" rowspan="1"><bold>160a</bold>
</td>
</tr>
<tr><td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">NE-3</td>
<td align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">0.048</td>
<td colspan="2" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">2.470</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>N.A. not applicable. Results were calculated by GraphPad Nonlinear regression analysis.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>
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