| Objective:Adenosine monophosphate(AMP)-activated kinase(AMPK)is a molecular energy sensor and a potential target for increasing the radiation sensitivity of tumor cells.Ionizing radiation(IR)activate AMPK through the DNA damage sensor ATM regulate radiosensitization of human cancer cells.However,using of AMPK direct activator of salicylic acid(SA)combined with IR whether to increase the radiosensitivity of cervical carcinoma cell,there is no report.We explored the regulation of AMPK associated signaling pathway by IR with SA and its role as a target for radiosensitization of cervical carcinoma cells.Methods:Ca Ski and HeLa cells were treated with IR and SA and subjected to proliferation,clonogenic,immunoblotting,cell cycle and apoptosis assays and histone H2AX was examined by fluorescence microscopy.Results:SA inhibited basal clonogenic survival and proliferation by dose(0.5-10mol/L)and time(24-72hr)dependent of Ca Ski and HeLa cells and sensitized Ca Ski to IR.SA increased Ca Ski cells DNA damage of y-H2AX foci after X-ray 8Gy irradiation and prolonged DNA repair.The drug enhanced apoptosis of Ca Ski cells after 48 hours SA alone(17.32%VS 8.52%,P=0.012)and augment IR-induced apoptosis(20.59%VS 13.39%,P=0.001).Compared with the control group,the effect of SA alone did not change Ca Ski cell cycle distribution significantly.Howerer,SA caused a redistribution of cells from G2-M phase(radiated cells)to G1-S phase(combined cells)of cell cycle when drug combine with IR.Detected by Western bloting,we found SA increasing phosphorylation levels of p-AMPKαThr172 and p-TSC2Ser1387 in Ca Ski cells;and SA significantly reduced the expression of p-mTORSer2448 induced by radiation(P=0.000).Conclusions:SA can increase the radiosensitivity of cervical carcinoma cells by regulating the AMPK/TSC2/mTOR signaling pathway.Targeting AMPK/TSC2/mTOR signaling pathway may provide a clinical approach to improve the efficacy of radiotherapy for cervical cancer. |
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