Autophagy inhibition of cancer stem cells promotes the efficacy of cisplatin against non-small cell lung carcinoma
Identifieur interne : 000869 ( Ncbi/Curation ); précédent : 000868; suivant : 000870Autophagy inhibition of cancer stem cells promotes the efficacy of cisplatin against non-small cell lung carcinoma
Auteurs : Chengcheng Hao ; Guiping Liu ; Guangliang TianSource :
- Therapeutic Advances in Respiratory Disease [ 1753-4658 ] ; 2019.
Abstract
Clinical treatment of non-small cell lung carcinoma (NSCLC) by cisplatin eventually results in drug resistance, which cancer stem cells and autophagy are believed to be involved in. In the present study, we aimed to explore the effect of autophagy-inhibited cancer stem cells in NSCLC.
Cancer stem cells were identified by CD133 expression levels detected by immunochemistry, real-time polymerase chain reaction, western blot, and flow cytometry. Stemness was detected by sphere-forming assays of tumor cells. Autophagy was determined by LC3-II expression at mRNA and protein levels. The effect of chloroquine (CQ) on autophagy was detected by real-time polymerase chain reaction, western blot and sphere-forming assay
Cisplatin (CDDP) treatment enhanced CD133+ cell ratios in clinical NSCLC specimens and NSCLC cell line A549. The CD133+ cells enriched by CDDP exhibited higher autophagy levels. Autophagy inhibition by CQ inhibited CD133+ stemness and promoted CDDP efficiency in A549 cells. In addition, the combination of CDDP and CQ treatment significantly inhibited autophagy levels and cancer stem cell proportions
Autophagy inhibition of cancer stem cells could promote the efficacy of cisplatin against NSCLC.
Url:
DOI: 10.1177/1753466619866097
PubMed: 31368411
PubMed Central: 6676261
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<author><name sortKey="Hao, Chengcheng" sort="Hao, Chengcheng" uniqKey="Hao C" first="Chengcheng" last="Hao">Chengcheng Hao</name>
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<author><name sortKey="Liu, Guiping" sort="Liu, Guiping" uniqKey="Liu G" first="Guiping" last="Liu">Guiping Liu</name>
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<author><name sortKey="Tian, Guangliang" sort="Tian, Guangliang" uniqKey="Tian G" first="Guangliang" last="Tian">Guangliang Tian</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Autophagy inhibition of cancer stem cells promotes the efficacy of cisplatin against non-small cell lung carcinoma</title>
<author><name sortKey="Hao, Chengcheng" sort="Hao, Chengcheng" uniqKey="Hao C" first="Chengcheng" last="Hao">Chengcheng Hao</name>
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<author><name sortKey="Liu, Guiping" sort="Liu, Guiping" uniqKey="Liu G" first="Guiping" last="Liu">Guiping Liu</name>
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<author><name sortKey="Tian, Guangliang" sort="Tian, Guangliang" uniqKey="Tian G" first="Guangliang" last="Tian">Guangliang Tian</name>
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<front><div type="abstract" xml:lang="en"><sec id="section1-1753466619866097"><title>Background:</title>
<p>Clinical treatment of non-small cell lung carcinoma (NSCLC) by cisplatin eventually results in drug resistance, which cancer stem cells and autophagy are believed to be involved in. In the present study, we aimed to explore the effect of autophagy-inhibited cancer stem cells in NSCLC.</p>
</sec>
<sec id="section2-1753466619866097"><title>Methods:</title>
<p>Cancer stem cells were identified by CD133 expression levels detected by immunochemistry, real-time polymerase chain reaction, western blot, and flow cytometry. Stemness was detected by sphere-forming assays of tumor cells. Autophagy was determined by LC3-II expression at mRNA and protein levels. The effect of chloroquine (CQ) on autophagy was detected by real-time polymerase chain reaction, western blot and sphere-forming assay <italic>in vitro</italic>
, and tumor growth in male NOD/SCID mice.</p>
</sec>
<sec id="section3-1753466619866097"><title>Results:</title>
<p>Cisplatin (CDDP) treatment enhanced CD133<sup>+</sup>
cell ratios in clinical NSCLC specimens and NSCLC cell line A549. The CD133<sup>+</sup>
cells enriched by CDDP exhibited higher autophagy levels. Autophagy inhibition by CQ inhibited CD133<sup>+</sup>
stemness and promoted CDDP efficiency in A549 cells. In addition, the combination of CDDP and CQ treatment significantly inhibited autophagy levels and cancer stem cell proportions <italic>in vitro</italic>
, and dramatically suppressed tumor growth compared with individual agents.</p>
</sec>
<sec id="section4-1753466619866097"><title>Conclusion:</title>
<p>Autophagy inhibition of cancer stem cells could promote the efficacy of cisplatin against NSCLC.</p>
</sec>
</div>
</front>
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