The Role And Its Mechanism Of Twist On Cervical Cancer EMT Induced By Hypoxic Microenvironment

[Objective]Investigate the role and its mechanism of Twist on cervical cancer EMT in hypoxia microenvironment, to provide an experimental basis of the targeted therapy and improve the therapeutic efficacy for cervical cancer.[Methods](1) The expression of HIF-la, Twist and Vimentin in middle and advanced stage cervical cancer tissue microarray chip which contains78cases were evaluated by immunohistochemistry method to study their relationship with clinical pathological characteristics and the correlation among them,(2) The Hela cells were treated with Cobalt chloride (CoCl2) to mimic the hypoxia microenvironment, the concentration and treatment duration of CoCl2were optimized by MTT method, which was used to detect the cell proliferation vitality.After6h treated with CoCl2, The morphologies of the Hela cells were studied by invert microscope,the migration ability of the cells were detect by Scratch test,and the expression of HIF-1α, Twist and Vimentin proteins in cells were measured by Immunofluorescence.[Results](1) The expression of HIF-la, twist and vimentin in78cases of cervical cancer tissue were54/78(69.2%),56/78(71.8%) and30/78(38.5%), respectively.The expression of HIF-la, Twist and vimentin in cervical cancer were significantly related to tumor histology type, FIGO stage, lymph node metastasis and differentiation degree respectively. With the increase of FIGO stage, the emergence of lymph node metastasis and the decrease of differentiation degree, the expression of HIF-la, Twist and vimentin increased gradually (P<0.05). The expression of HIF-la and vimentin in cervical cancer tissue has no correlation with patient age, But the expression of Twist in under-50age group was significantly higher than that of over-50age group (P<0.05).(2) The optimal CoC12concentration was150μmol/L and the optimum treatment time was six hours (P<0.05).(3) Under the hypoxia condition, the Hela cells obtained the morphological characteristics of stromal cells gradually. obvious morphological change can be observed by inverted microscope and the migration ability was significantly enhanced in Scratch test in Hela cells treated with150μmol/L CoCL2after6h (p<0.05).(4) The expression of HIF-la, Twist and vimentin of Hela cells in hypoxia microenvironment were significantly higher than those in the ordinary oxygen cells group (P<0.05), and there were significant positive Correlations among them (P<0.05).[Conclusions]Twist may play a key role on cervical cancer EMT in hypoxia microenvironment through HIF-la-Twist-vimentin pathway by up-regulation vimentin expression.