The Study Of Imatinib Mesylate On Radiosensitivity Of Human Cervical Cancer Cell Line Hela Under Normal And Hypoxia Growth Conditions

Object:To research the different doses of radiation,molecular targeted drug imatinib mesylate and paclitaxel inhibit the proliferation of human cervical cancer cell line Hela under normal and hypoxia growth conditions.This study was to investigate imatinib mesylate on radiosensitivity of Hela under normal and hypoxia growth conditions,and to explore the molecular mechanism of its mechanism of radiosensitization,which may provide a new direction for radiation therapy for cervical cancer. Method:Using hypoxic cell irradiation techniques to build hypoxia model of Hela; Radiation of Hela;MTT assay was used to analyze cell proliferation rate;Using the immunofluorescence to detect the expression of phosphorylation Platelet Derived Growth Factor Receptor-β(p-PDGFR-β),Vascular Endothelial Growth Fartor (VEGF) before and after treatment of imatinib mesylate under normal and hypoxia growth conditions.Results:The state of hypoxia could lead to morphological changes of Hela;After Hela receiving radiation it has the character that it could behaving after-accelated growth before growth inhibition;Different concentrations of imatinib and paclitaxel could inhibit the proliferation of Hela and both of them have dose-dependent effect;In the same conditions,using radiation therapy,imatinib mesylate or paclitaxel treatment into Hela which were at the state of 1 hour hypoxia,the proliferation was lowest of all; Subject to the same treatment,at the state of 2 hours of hypoxia,proliferation of Hela was significantly greater than the normal state and 1 hour of hypoxia,and the proliferation of Hela at normal state was greater than oxygen for 1 hour;In the state of hypoxia,imatinib mesylate could inhibit the proliferation of Hela when the concentration of it higher than 10μmol /L(P<0.05);The same thing happened to Hela under normal growth conditions when the concentration around 1μmol/L(P<0.05),this suggest that hypoxic cells may have a certain resistance to chemotherapeutic drugs;Low does of imatinib mesylate(0.1μmol/L)had a positive effect on the radiosensitivity of Hela under both normal and hypoxia growth conditions(P<0.05),and compared with paclitaxel,the radiation sensitizing effect has no significant difference(P>0.05);Hypoxic could induce PDGFR-βphosphorylation as well as enhance the expression of VEGF,imatinib mesylate could block the expression of PDGFR-βphosphorylation and inhibition the enhanced expression of VEGF on Hela under hypoxic conditions in vitro.Conclusion:Imatinib mesylate have radiation sensitizing effect on Hela under different growth conditions,and it may be used as a radiation sensitizer for the next phase of research;Imatinib mesylate could kill hypoxic cells by inhibit p-PDGFR-βand/or VEGF and reduced radiotherapy resistance of hypoxic cells;this contribution give us a clue that the PDGF / VEGF pathway may be one of the targets of imatinib mesylate's sensitization,providng a novel way for reduce the radiation resistance of tumor;In the early state of hypoxic,cells are in an instability condition and more easlier to be killed,once they enters into a stable state then they could behave resistance to chemotherapy and radiotherapy.