Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo
Identifieur interne : 000437 ( Main/Merge ); précédent : 000436; suivant : 000438Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo
Auteurs : Tianze Liu [République populaire de Chine] ; Lizi Jin [République populaire de Chine] ; Wenjing Lu [République populaire de Chine] ; Hairun Gan ; Zhidong Lin [République populaire de Chine] ; Miao Chen [République populaire de Chine] ; Jiani Liu [République populaire de Chine] ; Fan Zhang [République populaire de Chine] ; Siyang Wang [République populaire de Chine] ; Hongyu Zhang [République populaire de Chine] ; Wuguo Deng [République populaire de Chine] ; Hongtao Chen [République populaire de Chine]Source :
- Journal of Experimental & Clinical Cancer Research : CR [ 0392-9078 ] ; 2019.
Abstract
Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.
Six human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation assay; cell cycle and apoptosis were evaluated by flow cytometry; cell migration and invasion were measured by wound healing and transwell invasion assays respectively; protein expression was by detected by Western blot.
The growth inhibition effect of pemetrexed combined with icotinib on NSCLC cells were schedule-dependent in vitro
Sequential treatment of NSCLC cells with pemetrexed followed by icotinib had powerful antiproliferative effect, and it could become a novel effective combination therapy for NSCLC patients.
Url:
DOI: 10.1186/s13046-019-1133-z
PubMed: 30953548
PubMed Central: 6451286
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PMC:6451286Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo</title>
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<author><name sortKey="Lu, Wenjing" sort="Lu, Wenjing" uniqKey="Lu W" first="Wenjing" last="Lu">Wenjing Lu</name>
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<author><name sortKey="Gan, Hairun" sort="Gan, Hairun" uniqKey="Gan H" first="Hairun" last="Gan">Hairun Gan</name>
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Zhuhai, 519000 Guangdong Province China</nlm:aff>
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<author><name sortKey="Lin, Zhidong" sort="Lin, Zhidong" uniqKey="Lin Z" first="Zhidong" last="Lin">Zhidong Lin</name>
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<author><name sortKey="Chen, Miao" sort="Chen, Miao" uniqKey="Chen M" first="Miao" last="Chen">Miao Chen</name>
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Guangzhou, 510060 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Liu, Jiani" sort="Liu, Jiani" uniqKey="Liu J" first="Jiani" last="Liu">Jiani Liu</name>
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<author><name sortKey="Zhang, Fan" sort="Zhang, Fan" uniqKey="Zhang F" first="Fan" last="Zhang">Fan Zhang</name>
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Zhuhai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Wang, Siyang" sort="Wang, Siyang" uniqKey="Wang S" first="Siyang" last="Wang">Siyang Wang</name>
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Zhuhai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Zhang, Hongyu" sort="Zhang, Hongyu" uniqKey="Zhang H" first="Hongyu" last="Zhang">Hongyu Zhang</name>
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Zhuhai, 519000 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Zhuhai</wicri:regionArea>
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<author><name sortKey="Deng, Wuguo" sort="Deng, Wuguo" uniqKey="Deng W" first="Wuguo" last="Deng">Wuguo Deng</name>
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<institution>State Key Laboratory of Oncology in South China,</institution>
<institution>Sun Yat-sen University Cancer Center,</institution>
</institution-wrap>
Guangzhou, 510060 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Guangzhou</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chen, Hongtao" sort="Chen, Hongtao" uniqKey="Chen H" first="Hongtao" last="Chen">Hongtao Chen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="GRID">grid.452859.7</institution-id>
<institution>Department of Clinical Laboratory,</institution>
<institution>The Fifth Affiliated Hospital of Sun Yat-sen University,</institution>
</institution-wrap>
Zhuhai, 519000 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Zhuhai</wicri:regionArea>
</affiliation>
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<series><title level="j">Journal of Experimental & Clinical Cancer Research : CR</title>
<idno type="ISSN">0392-9078</idno>
<idno type="eISSN">1756-9966</idno>
<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">Six human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation assay; cell cycle and apoptosis were evaluated by flow cytometry; cell migration and invasion were measured by wound healing and transwell invasion assays respectively; protein expression was by detected by Western blot.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">The growth inhibition effect of pemetrexed combined with icotinib on NSCLC cells were schedule-dependent in vitro <italic>and</italic>
in vivo. Treatment with pemetrexed followed by icotinib (P-I) had significantly stronger anticancer ability than treatment with icotinib followed by pemetrexed (I-P) and concomitant treatment with pemetrexed and icotinib (P + I). Cell cycle analysis revealed that pemetrexed blocked cells in S phase, whereas icotinib arrested cells in G1 phase. We also found that icotinib markedly enhanced the pro-apoptotic activity of pemetrexed via cytochrome-C/Caspase/Bcl-2 signaling pathway. In addition, our results showed that pemetrexed alone increased the levels of p-EGFR, p-AKT and p-MAPK, which were inhibited by icotinib. Finally, we showed that the washout period of icotinib was no less than 96 h.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par4">Sequential treatment of NSCLC cells with pemetrexed followed by icotinib had powerful antiproliferative effect, and it could become a novel effective combination therapy for NSCLC patients.</p>
</sec>
</div>
</front>
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</TEI>
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