Caudatin Affects Cell Proliferation,Apoptosis And Migration In Cervical Carcinoma Cells Through Modulation Of TNFAIP1 Gene Expression

Cervical cancer and endometrial cancer are the most common malignant tumors of the female reproductive system,which threaten nearly a million of women’s health every year in the world.Currently,conventional treatment of cervical cancer and endometrial cancer is by surgery,chemotherapy and physical therapy.However,as the result of tumor migration,drug resistance,damage for normal tissue by chemotherapy and physical therapy,the effect of conventional treatment is usually unsatisfactory.Therefore,looking for an efficient and low-toxicity drug therapy has become a hot issue for researchers.Researches have shown that caudatin is a C21 steroidal glycosides monomer,which plays the role in inhibiting cell proliferation in gastric cancer,liver cancer and lung cancer and promoting apoptosis.Nonetheless,whether caudatin works out in the inhibition of cell proliferation in cervical cancer and endometrial cancer and the promotion of apoptosis has not been reported yet.Different concentrations of caudatin was applied by this paper to treat the cervical cancer cell line He La and endometrial cancer cell line HEC-1A.It had been found by MTT assay and colony formation assay that caudatin can inhibit cell proliferation.Through the flow cytometry analysis and Hochest33258 staining experiment,it can be seen that caudatin can promote He La and HEC-1A apoptosis.The result of western blotting assay indicates that the Bcl-2 family protein had abnormal expression with the increase of cytochrome C expression in He La and HEC-1A cell lines.The members of the cysteine protease family of Caspase 9,Caspase 3 and poly ADP-ribose polymerase(PARP)were activated.As was suggested by the cell scratch healing assay and cell microsphere experiment,caudatin can inhibit the migration rate of cells and the viability of cancer stem cells.Through the real-time quantitative PCR(q RT-PCR)test for 16 cases of pathological specimen tissues of cervical cancer,it was found that the expression level of TNFAIP1 was relatively low in poorly differentiated pathological tissues.After the He La and HEC-1A cell line treatment by different concentrations of caudatin,the result of the western blotting experiment test showed an increase of TNFAIP1 expression and a decrease of NFκB.Consistent results can be achieved in TNFAIP1 overexpression in He La and HEC-1A cells,indicating that caudatin was able to regulate the expression of TNFAIP1 and its downstream genes.Through an experiment in vivo,we had constructed xenografts tumor nude mice model of He La cells.After 14 days of intraperitoneal injection of drugs,it turned out that caudatin can inhibit the tumor growth.It was found by RT-PCR detection that the TNAIP1 m RNA level of tumors in the caudatin treatment group was high,but its NFκB m RNA level was relatively low,which indicated that caudatin can effectively inhibit tumor growth in vivo and regulate the expression of TNFAIP1 and its downstream genes.The results of this paper showed that caudatin can inhibit the cell proliferation,promote apoptosis,inhibit cell migration and regulate the expression of TNFAIP1 and its downstream genes in cervical cancer and endometrial cancer.Therefore,it can provide experimental evidence for the effectiveness of caudatin in clinical treatment of malignant tumors in the female reproductive system.