Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells.
Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells.
复制标题
自噬通过下调肝细胞癌细胞中的 Bad 和 Bim 抑制化疗诱导的细胞凋亡
DOI：
10.1038/srep05382
复制
发表时间：
2014-06-20
影响因子：
4.6
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Zhou Y;Sun K;Ma Y;Yang H;Zhang Y;Kong X;Wei L
包括缺血在内的肿瘤微环境越来越被认为是肿瘤发生过程中的关键因素。缺血引起的缺氧和营养缺乏广泛存在于实体瘤中。最近的研究表明，缺氧和营养缺乏通过诱导自噬导致化疗耐药，但其潜在机制仍不清楚。本研究旨在探讨低糖缺氧（LH）诱导的自噬在肝癌细胞化疗耐药中的作用。我们的结果表明，LH 诱导肝细胞癌细胞自噬并下调 Bad 和 Bim。自噬的抑制逆转了 LH 治疗期间这些促凋亡因子的减少。此外，在LH促进肝癌细胞化疗耐药的过程中，Bad和Bim也被自噬显着下调。此外，RNAi或Bad和Bim的过度表达可以分别显着减少或增加化疗诱导的细胞死亡。综上所述，这些数据表明 Bad 和 Bim 的下调在自噬诱导的肝细胞癌细胞化疗耐药中发挥着重要作用。
The tumor microenvironment, including ischemia, has been increasingly recognized as a critical factor in the process of tumor development. Hypoxia and nutrient deficiency resulting from ischemia widely exist in solid tumors. Recent studies have shown that hypoxia and nutrient deficiency contribute to chemoresistance by inducing autophagy, but the underlying mechanism remains unknown. This study aimed to explore the role of autophagy induced by low glucose and hypoxia (LH) in the chemoresistance of hepatocellular carcinoma cells. Our results demonstrated that LH induced autophagy and downregulated Bad and Bim in hepatocellular carcinoma cells. The inhibition of autophagy reversed the reduction of these pro-apoptotic factors during the LH treatment. Furthermore, Bad and Bim were also significantly downregulated by autophagy during the process that LH promoted the chemoresistance of hepatocellular carcinoma cells. In addition, RNAi or the overexpression of Bad and Bim can significantly reduce or increase chemotherapy-induced cell death, respectively. Taken together, these data indicate that the downregulation of Bad and Bim plays a significant role in the autophagy-induced chemoresistance of hepatocellular carcinoma cells.
登录
查看更多内容
缺氧中的自噬通过 Beclin1 依赖性方式在肝细胞癌中保护癌细胞免受营养剥夺诱导的细胞凋亡
影响因子：
4
作者：
Song, Jianrui;Guo, Xianling;Wei, Lixin
通讯作者：
Wei, Lixin
影响因子：
2.4
作者：
Kotsafti A;Farinati F;Cardin R;Cillo U;Nitti D;Bortolami M
通讯作者：
Bortolami M
影响因子：
78.5
作者：
Mathew, Robin;Karantza-Wadsworth, Vassiliki;White, Eileen
通讯作者：
White, Eileen
影响因子：
--
作者：
Briceno, Eduardo;Calderon, Alejandra;Sotelo, Julio
通讯作者：
Sotelo, Julio
影响因子：
--
作者：
Ma, Yi;Dai, HuiLi;Wang, LiMin
通讯作者：
Wang, LiMin