title: Autophagy inhibits chemotherapy-induced apoptosis through downregulating Bad and Bim in hepatocellular carcinoma cells.
abstract: 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.
authors.affiliation: Medical Sciences Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1] Medical Sciences Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China [2] Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Biobank, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Medical Sciences Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Haozheng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Hematology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Sciences Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Kong
authors.affiliation: 1] Medical Sciences Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China [2] Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D000072224:Bcl-2-Like Protein 11; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016896:Treatment Outcome; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein