The Study Of TNF-α And FOXO1 Affect On Cervical Cancer Cells

Cervical cancer is the second most common cancer, while the mortality rate rank top one in women worldwide. According to epidemiological data, the incidence of cervical cancer has increased in the recent years and has a tendency to become young. It has threatened the safety and healthy of women. It is very important for human being to cure cervical cancer. In fact, the patient with cervical cancer is incurable by the traditional therapy. It is important for us to find out a new way to cure cervical cancer. Current knowledge regarding the cause and pathogenesis of cervical cancer is expanding rapidly. There is an urgent need to understand the cell and molecular mechanism governing cervical tumorigenesis. FOXO1(Subfamily O1 of Forkhead transcription factors, FOXO1) has been shown to have a key role in a variety of biological processes, including the development of cancer. It acts as tumor suppressor in cervical cancer. The main results were as follows:(1) As a result, higher expression level of FOXO1 was observed in most normal cervix and CIN, whereas weak or undetectable FOXO1 expression was dominant in cervical cancer cases(P < 0.05). Moreover, the intensity of the FOXO1 staining in cervical cancer was on average significantly lower than that in normal cervix and CIN(P < 0.05). The deficient expression of FOXO1 is a mechanism of cervical cancer and the expression level of FOXO1 may be a measured standard for cervical cancer diagnose.(2) There was a significant correlation between FOXO1 positive expression and cell differentiation, FIGO grade, or lymphatic invasion in cervical cancer tissues(P < 0.05). In contrast, no significant correlation was observed between FOXO1 positive staining and patient’s age or pathological type in cervical cancer tissues(P > 0.05). The expression level of FOXO1 may be a measured standard for cervical cancer recovery.(3) As a result, the expression levels of FOXO1 in different cervical cancer cells were different(P < 0.05), showing that the mRNA and protein levels of FOXO1 in SiHa cells was the lowest while C-33 A cells was the most compared to in other cell lines(P < 0.05). There is no significant correlation between HPV affecting and the deficient expression of FOXO1(P < 0.05).(4) After SiHa cells transfecting an overexpression vector targeting human FOXO1 gene, cell viability was significantly decreased(P < 0.05) and cell proliferation was blocked(P < 0.05), accompanied by cell-cycle arrest in the G2/M and S phase. The overexpression of FOXO1 strongly induced an increase in Caspase-3, 8 and 9 mRNA activity(P < 0.05). In short, FOXO1 is a suppressor in cervical cancer and may be regard as a new target for gene therapy.(5) Adding different concentrations of TNF-α at the same time and adding the same concentration of TNF-α at different time into C-33 A cells, the expression level of FOXO1 was measured. Results showed that TNF-α increased the expression level of FOXO1 in a dose-dependent manner(P < 0.05) and in a time-dependent manner(P < 0.05).(6) The recombination of TNF-α and FOXO1 into C-33 A cells, cell viability was decreased(P < 0.05), cell cycle was blocked(P < 0.05), cell apoptotic rate and the mRNA expression levels of Caspase-3, 8 and 9 were increased(P < 0.05). Adding TNF-α into C-33 A cells transfected with FOXO1 siRNA, cell apoptotic rate and the mRNA expression levels of Caspase-3, 8 and 9 were not significantly recovered than adding TNF-α(P < 0.05).Taken together, the present study found that recombination of TNF-α and FOXO1 therapy for cervical cancer, providing a new theoretical basis for further understanding target gene anti-cancer action.