Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells.
Hypoxia commonly exists in solid tumors. Under such adverse conditions, adaptive responses including autophagy are usually provoked to promote cell survival. In our study, autophagy, a lysosomal-mediated degradation pathway, is demonstrated as a protective way to make hepatocellular carcinoma cells resistant to chemotherapy under hypoxia. Compared with normoxia, chemotherapeutic agent-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. However, when autophagy was inhibited by 3-MA or siRNA targeted Beclin 1, this reduction was reversed, i.e., chemoresistance was attenuated, which means autophagy mediates the chemoresistance under hypoxia. In conclusion, autophagy decreases hepatoma cells sensitization to chemotherapeutic agents by affecting their apoptotic potential.
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Jianrui
J
Song
Zengqiang
Z
Qu
Xianling
X
Guo
Qiudong
Q
Zhao
Xue
X
Zhao
Lu
L
Gao
Kai
K
Sun
Feng
F
Shen
Mengchao
M
Wu
Lixin
L
Wei
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000225:Adenine; D002945:Cisplatin