Abstract:

Objective To observe the effects of tumor suppressor gene VHL on the H₂O₂ induced oxidative stress of tumor cells and to primarily explore the molecular mechanism. Methods The expressions of vhl-1 gene of C.elegans and homologous gene VHL of cancer cells were silenced by RNAi. The death of C.elegans was morphologically analyzed after being treated by H₂O₂ of different concentrations. Cells were labeled by AnnexinⅤ and PI and the death of cells was analyzed by the flow cytometry. Then the phosphorylation level of pathway protein c-Jun N-terminal kinase (JNK) of oxidative stress was detected by the Western blotting and the molecular mechanism of effects of VHL on the oxidative stress of cells was analyzed. Results Compared to the control group, the sensitivity of C.elegans with silenced VHL gene towards H₂O₂ increased significantly and the mortality rate also increased significantly. These effects depended on the concentration gradient and treatment time of H₂O₂. The mortality rate of tumor cells with silenced VHL gene was not significantly different from that of wild type tumor cells. But the mortality rate of tumor cells with silenced VHL gene significantly increased and the phosphorylation level of JNK also increased after being treated by H₂O₂ of 250 μmol/L and 500 μmol/L. Conclusion Silencing the expression of VHL can increase the sensitivity of cells towards the oxidative stress induced by H₂O₂. The protective effect of VHL on the H₂O₂ induced oxidative stress is conserved in species.

Key words: oxidative stress, VHL, c-Jun N-terminal kinase