Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells

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作者
Yan Zhou
Kai Sun
Yi Ma
Haozheng Yang
Yuanliang Zhang
Xianming Kong
Lixin Wei
机构
[1] Shanghai Jiao Tong University,Medical Sciences Research Center, Ren Ji Hospital, School of Medicine
[2] The Second Military Medical University,Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital
[3] Ren Ji Hospital,Department of Biobank
[4] School of Medicine,Shanghai Institute of Hematology, Ruijin Hospital, School of Medicine
[5] Shanghai Jiao Tong University,undefined
[6] Shanghai Jiaotong University,undefined
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Scientific Reports | / 4卷
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摘要
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.
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