Research And Significance On CXXC4 Promoting Sensitivity To Chemotherapy Drugs In Epithelial Ovarian Cancer Cells

Background:Ovarian carcinoma is one of the most common and second most lethal gynecologic malignancy. An insidious progression, high malignancy and the inability to perform effective screening explain the late diagnosis at an advanced stage in 70% of cases with tumour cell spread throughout the abdominal cavity. The cytoreductive surgery and postoperative chemotherapy is the standard therapy for ovarian cancer of advanced stage. Optimal cytoreductive surgery followed by cisplatin/paclitaxel-based chemotherapy has been greatly improve the prognosis of early-stage ovarian cancer, while the prognosis of these advanced-stages thus remains grim, with the 5-year overall survival (OS) remain around 30%. A major contributor to the failure of chemotherapy is drug resistance(DR) of tumor cells towards chemotherapeutic drugs.Investigating the mechanisms of the DR, identifying drug targets and effective reversing the multiple drug resistance(MDR) were the keys of improving the cure rate for ovarian cancer. The multiple studies have shown that CXXC4 plays a growth suppressing function in progression, invasion of renal cell carcinoma and gastric cancer which through negatively regulating Wnt/β-catenin signaling and MAPK signaling. But the role of CXXC4 in the occurrence and development of ovarian cancer remains to be elucidated.Objective:The aim of this study is to detect the expression of CXXC4 in epithelial ovarian cancer cells. CXXC4 expression is regulated through plasmid transfection or RNA interference technology in order to evaluate the effect of CXXC4 on the proliferation and sensitivity to chemotherapy drugs in ovarian carcinoma cells and nomal ovarian epithelial cells,providing a novel molecular target to enhance the efficacy to chemotherapy in ovarian carcinoma cells.Methods:1. Protein and mRNA levels of CXXC4 were detected in nomal ovarian epithelial cells and ovarian carcinoma cells cultured in vitro by Western blot and Real-Time PCR respectively.2. According to the previous experimental results,The recombinant plasmid pcDNA3-CXXC4 and siRNA-CXXC4 were transfected into SKOV3, Caov3 cells and IOSE80 cells. CXXC4 gene overexpression and silence cell models were successfully constructed and their expression were verified via Western blot and Real-Time PCR respectively.3. CCK8 assay was used to evaluate the effect of CXXC4 on the proliferation and sensitivity to chemotherapy drugs. The role of CXXC4 on the sensitivity to chemotherapy drugs were described according to the IC50 values of ADM^ TA and DDP which were statistically analyzed by CCK8 assay.Results:1. The results of Western blot and Real-Time-PCR showed that, Protein and mRNA levels of CXXC4 were lower in ovarian carcinoma cells when compared with the normal ovarian epithelial cells.2. CCK8 assay shows that overexpression of CXXC4 inhibited the proliferation capacity at 72h post-transfection and promoted the sensitivity to chemotherapy drugs in SKOV3、Caov3 cells as the IC50 values of ADM、 TA and DDP deceased obviously.3. CCK8 assay shows that decreased CXXC4 could promote the proliferation capacity at 72h post-transfection and the chemo-resistance to chemotherapy drugs in normal ovarian epithelial cells as the IC50 values of ADM、 TA and DDP increased obviously.Conclusion:The CXXC4 could express in the ovarian cancer cell lines and the CXXC4 expression in ovarian cancer cells is association with the tumor occurrence and development. Overexpression of CXXC4 could inhibit the proliferation capacity and promote the sensitivity to chemotherapy drugs (ADM、TA and DDP) in ovarian carcinoma cells while decreasing CXXC4 in normal ovarian epithelial cells have the opposite effects. In conclusion, the expression of CXXC4 is associated with abnormal cell proliferating and chemotherapy sensitivity of ovarian cancer, suggesting it would be a potential biomarker to predict the efficacy or a molecular target to enhance the efficacy to chemotherapy in ovarian carcinoma cells.