Effect Of Nrf2 On Proliferation,invasion And Migration Of Cervical Cancer

Objective: To investigate the expression and clinical significance of Nrf2 and Keap1 protein in cervical cancer tissue and the effects on cell proliferation, invasion,migration,apoptosis of Nrf2 protein in cervical cancer cells. Method: Nrf2 and Keap1 were detected by immunohistochemistry in 201 samples of cervical tissues involving 66 normal cervixes,46 cervical intraepithelial neoplasis(CIN) and 89 invasive cervical cancer. Their clinical parameters were analyzed in cervical cancer. The expression of Nrf2 was examined by RT-PCR in SiHa,HeLa and C33 a cell lines. A sense Nrf2 recombinant plasmid was constructed and transfected to up-regulate Nrf2 in C33 a cells and transfected siRNA to sliencing Nrf2 in SiHa cellrespectively, Then Nrf2 examined by Western blot and RT-PCR. The proliferation and apotosis after transfection were examined by flow cytometry and the invasion and migration were examined by Transwell. Result:Compared with normal cervical epithelium and CIN tissues,Nrf2 was differently overexpressed in cervical cancer tissues(P<0.05). The Keap1 differently decreased in cervical cancer. There are significantly difference of Nrf2 expression was found with clinicopathologic parameters,such as lymph node metastasis,pathological grade and FIGO stage(P<0.05).Nrf2 mRNA and protein were differently overexpressed in SiHa,Hela and C33 a.Up-regulated Nrf2 promoted cell proliferation,invasion and migration in C33 a cells,Inhibited Nrf2 induces cell proliferation,invasion and migration,promoted cell apoptosis in SiHa cells. Conclusion: Nrf2 protein was strikingly over-expression in cervical cancer tissue and cells, Its level was tightly correlated with Keap1. Overexpressed Nrf2 promoted proliferation,invasion and migration in cervical cancer, but it had no effect on apoptosis.