Hydrogen Sulfide Contributes to Hypoxia-induced Radioresistance on Hepatoma Cells

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概要

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• Growing evidence has demonstrated that, as an endogenous signaling gasotransmitter, hydrogen sulfide (H2S) plays an important role in regulating numerous biological functions. The role of H2S in hypoxia-induced radioresistance on hepatoma cells was investigated in the present work. Results showed that, when HepG2 cells were maintained in hypoxia circumstances for 4 h, the cellular radioresistance was extensively increased so that the oxygen enhancement ratio of the survival fraction approached 2.68. Under this hypoxic condition, when the cells were treated with DL-propargylglycine (PPG) and aminooxyacetic acid (AOAA), a specific inhibitor of H2S synthase of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) respectively, radiation responses including cell killing, micronuclei (MN) formation, and caspase-3 activity were significantly enhanced. However, treatment of cells with low concentrations of NaHS (≤ 100 μM) protected cells from these radiation damages. Western bolting assay showed that CSE and CBS were over-expressed in the irradiated hypoxic cells in a dose dependent manner. Moreover, when the hypoxic HepG2 cells were treated with NaHS together with glibenclamide, a specific inhibitor of K+ATP channels, the role of exogenous H2S in radioprotection was partly eliminated. This study demonstrated that H2S contributed to hypoxia-induced radioresistance probably via the opening of K+ATP channels, which suggests that the endogenous H2S synthase could be a potential radiotherapeutic target for a hypoxic tumor.

• 2011-09-16

著者

• Shao C

  Research Center For Nano-device And System Nagoya Institute Of Technology

• Shao Chunlin

  Institute Of Radiation Medicine Fudan University

• ZHANG Jianghong

  Institute of Radiation Medicine, Fudan University

• PAN Yan

  Institute of Radiation Medicine, Fudan University

• Pan Yan

  Institute Of Radiation Medicine Fudan University

• Xie Yuexia

  Institute Of Radiation Medicine Fudan University

• Xu Yanwu

  Department Of Biochemistry The Basic Medical Academy Of Shanghai University Of Traditional Chinese M

• Zhang Jianghong

  Institute Of Radiation Medicine Fudan University

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