title: Autophagy in hypoxia protects cancer cells against apoptosis induced by nutrient deprivation through a Beclin1-dependent way in hepatocellular carcinoma.
abstract: Oxygen deficiency and nutrient deprivation widely exists in solid tumors because of the poor blood supply. However, cancer cells can survive this adverse condition and proliferate continuously to develop. To figure out the way to survive, we investigated the role of autophagy in the microenvironment in hepatocellular carcinoma. In order to simulate the tumor microenvironment more veritably, cells were cultured in oxygen-nutrient-deprived condition following a hypoxia preconditioning. As a result, cell death under hypoxia plus nutrient deprivation was much less than that under nutrient deprivation only. And the decreased cell death mainly attributed to the decreased apoptosis. GFP-LC3 and electron microscopy analysis showed that autophagy was significantly activated in the period of hypoxia preconditioning. However, autophagic inhibitor-3-MA significantly abrogated the apoptosis reduction in hypoxia, which implied the involvement of autophagy in protection of hepatocellular carcinoma cells against apoptosis induced by starvation. Furthermore, Beclin 1 was proved to play an important role in this process. siRNA targeting Beclin 1 was transfected into hepatocellular carcinoma cells. And both data from western blot detecting the expression of LC3-II and transmission microscopy observing the accumulation of autophagosomes showed that autophagy was inhibited obviously as a result of Beclin 1 knockdown. Besides, the decreased apoptosis of starved cells under hypoxia was reversed. Taken together, these results suggest that autophagy activated by hypoxia mediates the tolerance of hepatocellular carcinoma cells to nutrient deprivation, and this tolerance is dependent on the activity of Beclin 1.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Jianrui
authors.initials: J
authors.lastname: Song
authors.forename: Xianling
authors.initials: X
authors.lastname: Guo
authors.forename: Xuqin
authors.initials: X
authors.lastname: Xie
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Weijie
authors.initials: W
authors.lastname: Deng
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D001343:Autophagy; D000071186:Beclin-1; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D034741:RNA, Small Interfering
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D034741:RNA, Small Interfering