Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Cancer Lett. 2012 Jan 28;314(2):232-43. doi: 10.1016/j.canlet.2011.09.034. Epub 2011 Oct 2.
The function of autophagy in cisplatin-treated cancer cells is not fully understood. Cisplatin treatment induced degradation of ubiquitinated proteins by autophagy, which reduced apoptosis induced by endoplasmic reticulum (ER) stress and downregulated the mitochondrial pathway of apoptosis. Inhibition of autophagy using 3-methyladenine (3-MA) or chloroquine (CQ) increased the levels of intracellular misfolded proteins, which enhanced cellular apoptosis. We found that tunicamycin, an ER stress inducer, augmented cisplatin cytotoxicity by upregulating ER stress-mediated apoptosis. Our data indicates that autophagy plays an important role in preventing cisplatin-induced apoptosis in HeLa cells, thus inhibition of autophagy may improve cisplatin chemotherapy.
自噬在顺铂处理的癌细胞中的功能尚未完全阐明。顺铂处理通过自噬诱导泛素化蛋白的降解，从而减少内质网（ER）应激诱导的细胞凋亡，并下调线粒体凋亡途径。使用 3-甲基腺嘌呤（3-MA）或氯喹（CQ）抑制自噬会增加细胞内错误折叠蛋白的水平，从而增强细胞凋亡。我们发现，衣霉素，一种内质网应激诱导剂，通过上调内质网应激介导的细胞凋亡来增强顺铂的细胞毒性。我们的数据表明，自噬在防止 HeLa 细胞中顺铂诱导的细胞凋亡中起重要作用，因此抑制自噬可能会改善顺铂化疗。
