MCL-1 is the key target of adjuvant chemotherapy to reverse the cisplatin-resistance in NSCLC
作者： Jun Ma , Zhenxian Zhao , Kaiming Wu , Zhe Xu , Kuanzhi Liu
DOI: 10.1016/J.GENE.2016.04.054
关键词: Cancer research 、 Immunology 、 Treatment of lung cancer 、 Targeted therapy 、 Programmed cell death 、 Obatoclax 、 Apoptosis 、 Cisplatin 、 Chemotherapy 、 Cancer cell 、 Biology
摘要: Cisplatin is one of the most effective chemotherapeutic agents for treatment lung cancer. However, acquired resistance occurred in cancer cells limits clinical application cisplatin. MCL-1, which an important member pro-survival Bcl-2 family, plays a critical role multidrug (MDR). The aim present study to investigate value Pan-Bcl-2 inhibitor as sensitizer chemotherapy cisplatin-resistant non-small cell (NSCLC) cells. We found obatoclax but not ABT-737 significantly decreased IC50 (half maximal inhibitory concentration) cisplatin NSCLC Furthermore, we demonstrated that mechanism obatoclax-promoted death induced by was dependent on inhibition couldn't be inhibited target obatoclax. Moreover, MCL-1 recovered function NOXA and BAK cells, leading promotion mitochondrial apoptosis Interestingly, our date indicated also reversed cross-resistance Therefore, targeted therapy with inhibitors, such obatoclax, may represent novel strategy therapy.
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