Blocking autophagy magnifies MK-2206-induced DNA damage in SGC-7901 cells |
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| Authors: | ZHANG Cui JIANG Wen-yan WU Yu-mei ZHUANG Meng-wei WANG Xi-shuang JIAO Peng |
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| Institution: | 1. School of Life Sciences, Taishan Medical University, Tai'an 271016, China;
2. Department of Pharmacy, Office Hospital of Shengli Oil Field, Dongying 257000, China;
3. Life Sciences Research Centre, Taishan Medical University, Tai'an 271016, China |
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| Abstract: | AIM: To investigate the effect of MK-2206, an inhibitor of protein kinase B(Akt), on the DNA damage of SGC-7901 cells.METHODS: SGC-7901 cells were treated with different concentrations of MK-2206, and phosphorylated histone H2AX(γ-H2AX) foci formation was detected by immunofluorescence staining. Western blot analysis was used to exam the levels of DNA damage-related protein. The expression of LC3-Ⅱ was determined to evaluate the change of autophagy.RESULTS: MK-2206 treatment increased the formation of γ-H2AX foci and histone H2AX phosphorylation in the SGC-7901 cells. The levels of DNA damage response protein were also increased. In addition, MK-2206-treated SGC-7901 cells increased the expression of LC3-II, a hallmark of autophagy. Inhibition of autophagy significantly enhanced MK-2206-mediated histone H2AX phosphorylation.CONCLUSION: MK-2206 induces DNA damage and autophagy in SGC-7901 cells. Blocking autophagy potentiates the response of MK-2206-induced DNA damage. |
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| Keywords: | MK-2206 Akt inhibitor DNA damage γ-H2AX Cell autophagy |
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