Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis
Identifieur interne : 000595 ( Pmc/Curation ); précédent : 000594; suivant : 000596Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis
Auteurs : Nan Zhang [République populaire de Chine] ; Fu Peng [République populaire de Chine] ; Yujia Wang [République populaire de Chine] ; Li Yang [République populaire de Chine] ; Fengbo Wu [République populaire de Chine] ; Xiaoyun Wang [République populaire de Chine] ; Cui Ye [République populaire de Chine] ; Bo Han [République populaire de Chine] ; Gu He [République populaire de Chine]Source :
- International Journal of Biological Sciences [ 1449-2288 ] ; 2020.
Abstract
Colorectal carcinoma (CRC) is the third most common malignant tumor pathology worldwide. Despite progress in surgical procedures and therapy options, CRC is still a considerable cause of cancer-related mortality. In this study, we tested the antitumor effects of shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well as
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DOI: 10.7150/ijbs.36955
PubMed: 31892852
PubMed Central: 6930377
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Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yujia" sort="Wang, Yujia" uniqKey="Wang Y" first="Yujia" last="Wang">Yujia Wang</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Li" sort="Yang, Li" uniqKey="Yang L" first="Li" last="Yang">Li Yang</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Fengbo" sort="Wu, Fengbo" uniqKey="Wu F" first="Fengbo" last="Wu">Fengbo Wu</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 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611137, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137</wicri:regionArea></affiliation></author><author><name sortKey="Han, Bo" sort="Han, Bo" uniqKey="Han B" first="Bo" last="Han">Bo Han</name><affiliation wicri:level="1"><nlm:aff id="A1">State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137</wicri:regionArea></affiliation></author><author><name sortKey="He, Gu" sort="He, Gu" uniqKey="He G" first="Gu" last="He">Gu He</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31892852</idno><idno type="pmc">6930377</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930377</idno><idno type="RBID">PMC:6930377</idno><idno type="doi">10.7150/ijbs.36955</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000595</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000595</idno><idno type="wicri:Area/Pmc/Curation">000595</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000595</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis</title><author><name sortKey="Zhang, Nan" sort="Zhang, Nan" uniqKey="Zhang N" first="Nan" last="Zhang">Nan Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Fu" sort="Peng, Fu" uniqKey="Peng F" first="Fu" last="Peng">Fu Peng</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yujia" sort="Wang, Yujia" uniqKey="Wang Y" first="Yujia" last="Wang">Yujia Wang</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Li" sort="Yang, Li" uniqKey="Yang L" first="Li" last="Yang">Li Yang</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Fengbo" sort="Wu, Fengbo" uniqKey="Wu F" first="Fengbo" last="Wu">Fengbo Wu</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xiaoyun" sort="Wang, Xiaoyun" uniqKey="Wang X" first="Xiaoyun" last="Wang">Xiaoyun Wang</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author><author><name sortKey="Ye, Cui" sort="Ye, Cui" uniqKey="Ye C" first="Cui" last="Ye">Cui Ye</name><affiliation wicri:level="1"><nlm:aff id="A1">State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137</wicri:regionArea></affiliation></author><author><name sortKey="Han, Bo" sort="Han, Bo" uniqKey="Han B" first="Bo" last="Han">Bo Han</name><affiliation wicri:level="1"><nlm:aff id="A1">State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137</wicri:regionArea></affiliation></author><author><name sortKey="He, Gu" sort="He, Gu" uniqKey="He G" first="Gu" last="He">Gu He</name><affiliation wicri:level="1"><nlm:aff id="A2">State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041</wicri:regionArea></affiliation></author></analytic><series><title level="j">International Journal of Biological Sciences</title><idno type="eISSN">1449-2288</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Colorectal carcinoma (CRC) is the third most common malignant tumor pathology worldwide. Despite progress in surgical procedures and therapy options, CRC is still a considerable cause of cancer-related mortality. In this study, we tested the antitumor effects of shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well as <italic>in vitro</italic> and <italic>in vivo</italic> antitumor effects of shikonin in CRC cells were determined by an integrative protocol including quantitative proteomics, RT-PCR, western blotting, RNA interference and overexpression, apoptosis and autophagy assays, etc. Galectin-1 was a potential target of shikonin from the iTRAQ-based proteomic analysis in shikonin-treated SW620 cell. The overexpression and RNA silencing of galectin-1 in two CRC cells suggested that the shikonin sensitivity was correlation to galectin-1 levels. The ROS accumulation induced by shikonin was important to the formation of galectin-1 dimers. Dimer galectin-1 was found to be associated with the activation of JNK and downstream apoptosis or autophagy. Moreover, through functional <italic>in vitro</italic> studies, we showed that differences in galectin-1 level affected tumor cell proliferation, migration, and invasion. In summary, shikonin induced CRC cells apoptosis and autophagy by targeting galectin-1 and JNK signaling pathway both <italic>in vitro</italic> and <italic>in vivo</italic>, which suggested a potential novel therapy target for CRC.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author><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="Siegel, Rl" uniqKey="Siegel R">RL Siegel</name></author><author><name sortKey="Torre, La" uniqKey="Torre L">LA Torre</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonzalez Pons, M" uniqKey="Gonzalez Pons M">M Gonzalez-Pons</name></author><author><name sortKey="Cruz Correa, M" uniqKey="Cruz Correa M">M 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Biol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Biol. Sci</journal-id><journal-id journal-id-type="publisher-id">ijbs</journal-id><journal-title-group><journal-title>International Journal of Biological Sciences</journal-title></journal-title-group><issn pub-type="epub">1449-2288</issn><publisher><publisher-name>Ivyspring International Publisher</publisher-name><publisher-loc>Sydney</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31892852</article-id><article-id pub-id-type="pmc">6930377</article-id><article-id pub-id-type="doi">10.7150/ijbs.36955</article-id><article-id pub-id-type="publisher-id">ijbsv16p0147</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Nan</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Peng</surname><given-names>Fu</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yujia</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Li</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Fengbo</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Xiaoyun</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ye</surname><given-names>Cui</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Bo</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Gu</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib></contrib-group><aff id="A1"><label>1</label>State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China</aff><aff id="A2"><label>2</label>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu 610041, China</aff><author-notes><corresp id="FNA_envelop">✉ Corresponding authors: Bo Han (<email>hanbo@cdutcm.edu.cn</email>); Gu He (<email>hegu@scu.edu.cn</email>); Tel: +86-28-85503817</corresp><fn fn-type="equal" id="FNA_star"><p>*These authors contributed equally.</p></fn><fn fn-type="COI-statement"><p>Competing Interests: The authors have declared that no competing interest exists.</p></fn></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>1</day><month>1</month><year>2020</year></pub-date><volume>16</volume><issue>1</issue><fpage>147</fpage><lpage>161</lpage><history><date date-type="received"><day>4</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>20</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>© The author(s)</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>). See <ext-link ext-link-type="uri" xlink:href="http://ivyspring.com/terms">http://ivyspring.com/terms</ext-link> for full terms and conditions.</license-p></license></permissions><abstract><p>Colorectal carcinoma (CRC) is the third most common malignant tumor pathology worldwide. Despite progress in surgical procedures and therapy options, CRC is still a considerable cause of cancer-related mortality. In this study, we tested the antitumor effects of shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well as <italic>in vitro</italic> and <italic>in vivo</italic> antitumor effects of shikonin in CRC cells were determined by an integrative protocol including quantitative proteomics, RT-PCR, western blotting, RNA interference and overexpression, apoptosis and autophagy assays, etc. Galectin-1 was a potential target of shikonin from the iTRAQ-based proteomic analysis in shikonin-treated SW620 cell. The overexpression and RNA silencing of galectin-1 in two CRC cells suggested that the shikonin sensitivity was correlation to galectin-1 levels. The ROS accumulation induced by shikonin was important to the formation of galectin-1 dimers. Dimer galectin-1 was found to be associated with the activation of JNK and downstream apoptosis or autophagy. Moreover, through functional <italic>in vitro</italic> studies, we showed that differences in galectin-1 level affected tumor cell proliferation, migration, and invasion. In summary, shikonin induced CRC cells apoptosis and autophagy by targeting galectin-1 and JNK signaling pathway both <italic>in vitro</italic> and <italic>in vivo</italic>, which suggested a potential novel therapy target for CRC.</p></abstract><kwd-group><kwd>Shikonin</kwd><kwd>Colorectal carcinoma</kwd><kwd>Galectin-1</kwd><kwd>apoptosis</kwd><kwd>autophagy</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><p>(A) The cell proliferation inhibition (%) of a panel of cancer cell lines incubated by shikonin for 24h; The green color label for 2.5μM shikonin-treated group, while the blue color label for 5μM shikonin-treated group and red color label for 10μM; (B) The cell proliferation inhibition curves of SW620 and HCT116 colorectal carcinoma cells after shikonin incubation; (C) The colony formation of SW620 and HCT116 cells after shikonin incubation; (D) The nuclei morphological changes of SW620 and HCT116 cells incubated by shikonin with Hoechst33258 staining; (E) The apoptosis assays of SW620 and HCT116 cells incubated by shikonin. (*, p < 0.05, ****, p < 0.0001)</p></caption><graphic xlink:href="ijbsv16p0147g001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p>(A) The formation of GFP-LC3 fluorescent puncta induced by shikonin incubation; (B) The autophagic vacuoles induced by shikonin incubation in SW620 and HCT116 cells detected by TEM.</p></caption><graphic xlink:href="ijbsv16p0147g002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p>iTRAQ-based analysis of shikonin-related signaling pathways. (A) (B) (C) Cluster enrichment of the differentially expressed proteins in shikonin-treated SW620 cell; (D) Real-time PCR analysis of different levels of mRNA in shikonin (SK)-treated SW620 cell; (E) Target identification for interaction between shikonin (SK) and galectin-1 by DARTs. Cell lysates and recombinant galectin-1 were both incubated with 400μM, 800μM and 1200μM shikonin or DMSO.</p></caption><graphic xlink:href="ijbsv16p0147g003"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><p>(A) Western bloting of apoptotic markers; (B-C) Quantification of apoptotic markers in panel A for SW620 and HCT116 cells; (D) Western bloting of p62 and LC3 in total lysates of SW620 and HCT116 cells after treated with shikonin (SK) alone or the combination of shikonin (SK) and autophage activator or inhibitor; (E) Quantification of autophagic markers in panel D. “Rapa” represents the autophage activator rapamycin. “3-MA” represents the autophage inhibitor 3-methyladenine. “HCQ” represents hydroxychloroquine and “BA” represents bafliomycin and both of HCQ and BA are autophage inhibitors can inhibit the degradation of autophagolysosomes.</p></caption><graphic xlink:href="ijbsv16p0147g004"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><p>(A) Flow cytometry based on DCFH-DA staining to assess levels of ROS in two CRC cell lines after treated with shikonin (SK) alone or the conmbination of shikonin (SK) and NAC; (B) Western bloting of p62 and LC3 in total lysates of SW620 and HCT116 cells after treated with shikonin (SK) alone or the combination of shikonin (SK) and NAC; (C) Western bloting of apoptotic markers in total lysates of SW620 and HCT116 cells after treated with shikonin (SK) alone or the combination of shikonin (SK) and NAC.</p></caption><graphic xlink:href="ijbsv16p0147g005"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><p>(A) Western bloting of galectin-1 in total lysates of SW620 and HCT116 cells after treated with shikonin; (B) Cell inhibition ratios in SW620 and galectin-1 overexpressed SW620 (SW620-Gal1); (C) Cell inhibition ratios in HCT116 and galectin-1 overexpressed HCT116 (SW620-Gal1); (D) Quantification of flow cytometry analysis to assess total apoptotic ratios in SW620 and SW620-Gal1 after treated with shikonin; (E) Quantification of flow cytometry analysis to assess total apoptotic ratios in HCT116 and HCT116-Gal1 after treated with shikonin; (F) Laser confocal microscopy images; (G-I) Changes in expression of Dimer-gal1, gal-1, p62, LC3 and Cyto c after treatment with si-gal1, shikonin (SK) or both; (J-K) Changes in expression of Dimer-gal1 and gal-1 after treatment with shikonin (SK), NAC or both; (L-M) Changes in expression of EMT markers after treatment with si-gal1, shikonin (SK) or both.</p></caption><graphic xlink:href="ijbsv16p0147g006"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><p>(A) Western bloting of Dimer-gal1, gal-1, LC3 and p62 after treatment with shikonin (SK) and JNK inhibitor (SP); (B) Western bloting of apoptotic markers after treatment with shikonin (SK) and JNK inhibitor (SP); (C) Western bloting of JNK and p-JNK after treatment with shikonin (SK) and NAC; (D) Western bloting of JNK and p-JNK after treatment with shikonin (SK) and siRNA for galectin-1 (si-gal); (E) Laser confocal microscopy images of cell location of JNK and mitochondria.</p></caption><graphic xlink:href="ijbsv16p0147g007"></graphic></fig><fig id="F8" position="float"><label>Figure 8</label><caption><p>(A) SW620 xenograft tumor volume after treatment with saline (control) or shikonin (SK). Results are mean ± SD; **P < 0.01 and *P < 0.05 vs control (N = 5); (B) Immunohistochemistry to evaluate expression of ATG5, Beclin-1, LC3, galectin-1, Ki67 and Tunel in tumour sections. Quantitation is shown on the right.</p></caption><graphic xlink:href="ijbsv16p0147g008"></graphic></fig><fig id="F9" position="float"><label>Figure 9</label><caption><p>The plausible molecular mechanism of shikonin in colorectal carcinoma cells.</p></caption><graphic xlink:href="ijbsv16p0147g009"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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