The Study Of Trichostatin A On Radiosensitivity Of Human Cervical Carcinoma Cell Line Hela Under Hypoxic Conditions

Object: To research the different doses of radiation, molecular targeted drug trichostatin A inhibit the proliferation of human cervical carcinoma cell line Hela under normoxic and hypoxic conditions. This study was to investigate trichostatin A on radiosensitivity of Hela under normoxic and hypoxic conditions, and to explore the molecular mechanism of its mechanism of radiosensitization, which may provide a new direction for radiation therapy for cervical carcinoma.Method: Hypoxia was induced in Hela cells by N2 treatment; Methylthiazolyl tetrazolium (MTT) assay was used to analyze cell growth inhibition rate, the 50% inhibition concentration (IC50) and 10% inhibition concentration (IC10) were calculated by SPSS13.0 software; Hela cells under normoxic conditions were assayed for radiosentizing effect of TSA combining different low dose of fractionated radiotherapy were detected by MTT assay; Hela cells under hypoxic conditions were assayed for clonogenic survival, and utilized the〝Multitarget-single hitting〞model to fit the cell survival curve, determined the radiosensitization effect induced by 10% inhibition concentration of TSA; The expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) proteins were detected by immunocytochemistry before and after treatment of trichostatin A under normoxic and hypoxic conditions.Results: TSA siginificantly inhibited the proliferation of Hela cells in a dose-and time-dependent manner under normoxic and hypoxic conditions; the 50% inhibition concentration and 10% inhibition concentration under normoxic conditions were 0.031μmol/L and 0.587μmol/L; the 50% inhibition concentration and 10% inhibition concentration under hypoxic conditions were 0.076μmol/L and 0.947μmol/L. When exposed to TSA for 24h, the SER of Hela cells under normoxic conditions were 1.69, SERS of IC10 TSA combining 2.0Gy/time, 1.0Gy/time(×2), 0.5Gy/time(×4) fractionated radiotheerapy groups were 1.45, 1.64, 1.96; When exposed to TSA for 24h, the SER_D0, SER_Dq and SER_SF2 of Hela cells under hypoxic conditions were 1.48, 1.80 and 1.34; Immunocytochemistry staining revealed that the expression leavls of HIF-1αand VEGF proteins in Hela cells under hypoxic conditions were evidently higher than those in Hela cells under nomoxic conditions. However, TSA siginificantly down-regulatled the expression of HIF-1αand VEGF proteins in Hela cells under hypoxicconditions. Conclusion: Trichostatin A have radiation sensitizing effect on Hela cells undernormoxic and hypoxic conditions, and it may be used as a radiation sensitizer for the next phase of research; TSA can significantly enhance radiosentivity in Hela cells under hypoxic conditions perhaps by down-regulating the expression of HIF-1αand VEGF proteins; this contribution give us a clue that the HIF-1α/ VEGF pathway may be one of the targets of Trichostatin A to radiosensitization.