Radiosensitization of phosphatidylinositol 3-1dnase inhibitor on esophageal cancer cell line Eca-109 and its mechanism
AIM: To investigate the radiosensitization effect and possible mechanism of PI3K inhibitor-LY294002 on esophageal cancer cell line Eca-109. METHODS: MTT assay was used to test the inhibitory effect of LY294002 on tumor cell proliferation and clonogenic assay was performed to determine the radiosensitization effect of LY294002 on Eca-109 cell line. RT-PCR was used to detect the expression of DNA double-strand break repair gene--DNA-PKcs mRNA and cell cycle was detected by flow cytometry. RESULTS: PI3K inhibitor LY294002 inhibited Eca-109 cell line proliferation in a dose-dependent manner. A low-cytotoxic concentration of LY294002 at 10 μmol/L significantly reduced the cloning efficiency of Eca-109 cell and the radiosensitization enhancement ratio was 1.58. Expression of DNA-PKcs mRNA in the drug group was inhibited compared with that in the control group, with no statistically significance. Expression of DNA-PKcs mRNA in the radiation group was higher than that in the control group (P ＜ 0.05), but it was significantly reduced in the LY294002 + radiation group compared with that in the radiation group(P ＜ 0.05). No statistical difference was found in the G2 phase cell proportion between drug group and control group. C2 phase cell proportion in the radiation group was significantly higher than that in control group (P ＜ 0.01), but it was significantly reduced in the LY294002 + radiation group compared with that in the radiation group (P ＜ 0.05). CONCLUSION: PI3K inhibitor LY294002 enhances the radiosensitivity of human esophageal cancer cell line Eca-109 and this effect is possibly associated with the expression inhibition of DNA-PKcs mRNA and abrogation of radiation-induced G2 phase arrest.
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