ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells.
ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells.
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DOI：
10.3892/or.2016.4680
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发表时间：
2016-05
期刊：
影响因子：
4.2
通讯作者：
Ma Z
中科院分区：
文献类型：
--
作者：
Shi S;Tan P;Yan B;Gao R;Zhao J;Wang J;Guo J;Li N;Ma Z
顺铂[cis-diamminedichloropatinumII（CDDP）]是治疗包括肺癌在内的癌症的最经典和有效的化疗药物之一。然而，顺铂耐药性的存在降低了其疗效，并限制了其在临床上的使用。本研究旨在探讨肺癌顺铂耐药的内质网应激和自噬机制。本研究检测顺铂对肺癌细胞株A549和H460细胞活力、内质网应激和自噬的影响。我们还测试了ER应激和自噬对顺铂诱导的细胞凋亡的影响。结果表明，顺铂诱导肺癌细胞凋亡、内质网应激和自噬。此外，4-苯基丁酸（4-PBA）或牛磺熊去氧胆酸钠（TUDC）抑制ER应激可增强顺铂诱导的人肺癌细胞凋亡。同时，联合应用自噬抑制剂3-甲基腺嘌呤（3-MA）或氯喹（CQ）进一步增加顺铂诱导的人肺癌细胞凋亡。本研究提供了一种新的治疗策略-顺铂联合自噬抑制剂或ER应激抑制剂导致人肺癌细胞凋亡增加。
Cisplatin [cis-diamminedichloroplatinum II (CDDP)] is one of the most classical and effective chemotherapeutic drugs for the treatment of cancers including lung cancer. However, the presence of cisplatin resistance in cancer lowers its curative effect and limits its usage in the clinic. The aim of the present study was to investigate the underlying mechanisms of cisplatin resistance in lung cancer involving endoplasmic reticulum (ER) stress and autophagy. In the present study, we detected the effect of cisplatin on cell viability, ER stress and autophagy in lung cancer cell lines A549 and H460. We also tested the effects of ER stress and autophagy on apoptosis induced by cisplatin. The results showed that cisplatin induced apoptosis, ER stress and autophagy in lung cancer cell lines. In addition, the inhibition of ER stress by 4-phenylbutyric acid (4-PBA) or tauroursodeoxycholic acid sodium (TUDC) enhanced cisplatin-induced apoptosis in the human lung cancer cells. Meanwhile, combination treatment with the autophagic inhibitor 3-methyladenine (3-MA) or chloroquine (CQ) further increased the apoptosis induced by cisplatin in the human lung cancer cells. The present study provides a novel treatment strategy - cisplatin in combination with an autophagic inhibitor or an ER stress inhibitor leads to increased apoptosis in human lung cancer cells.