Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells
Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells
复制标题
靶向自噬增强化疗诱导的肝癌细胞凋亡和增殖抑制
DOI：
10.1016/j.canlet.2012.03.002
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发表时间：
2012-07-28
期刊：
影响因子：
9.7
通讯作者：
Wei, Li-xin
中科院分区：
文献类型：
--
作者：
Guo, Xian-ling;Li, Ding;Wei, Li-xin
诱导细胞死亡和抑制细胞生长是癌症治疗的主要目标。在此，我们评估了自噬在人肝癌（HCC）细胞系化疗耐药性中的作用，重点是其与细胞凋亡和增殖的相互作用。在这项研究中，化疗药物（顺铂或5 FU）诱导自噬体在三个人肝癌细胞系的形成和上调自噬蛋白LC 3-II的表达。通过3-甲基腺嘌呤或si-beclin 1抑制自噬增加了HCC细胞中化疗诱导的凋亡。同时，自噬被抑制后，肝癌细胞线粒体膜电位的损伤也增加。此外，当用化疗治疗时，抑制自噬减少了HCC细胞的克隆形成和受损的细胞生长。自噬抑制剂（氯喹）和化疗的共同管理显着抑制小鼠异种移植肿瘤模型中的肿瘤生长，更大程度的细胞凋亡和受损的肿瘤细胞增殖。这项研究表明，自噬是一个潜在的新的目标，以提高常规化疗药物对肝癌的治疗效率。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Induction of cell death and inhibition of cell growth are the main targets of cancer therapy. Here we evaluated the role of autophagy on chemoresistance of human hepatocarcinoma (HCC) cell lines, focusing on its crosstalk with cell apoptosis and proliferation. In this study, a chemotherapeutic agent (cisplatin or 5FU) induced the formation of autophagosomes in three human HCC cell lines and upregulated the expression of autophagy protein LC3-II. Inhibition of autophagy by 3-methyladenine or si-beclin 1 increased chemotherapy-induced apoptosis in HCC cells. Meanwhile, increased damage of the mitochondrial membrane potential was also observed in HCC cells when autophagy was inhibited. Furthermore, inhibition of autophagy reduced clone formation and impaired cell growth of HCC cells when treated with chemotherapy. Co-administration of an autophagy inhibitor (chloroquine) and chemotherapy significantly inhibited tumor growth in a mouse xenograft tumor model, with greater extent of apoptosis and impaired proliferation of tumor cells. This study suggests that autophagy is a potential novel target to improve therapy efficiency of conventional chemotherapeutics towards HCC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.