| Objective: To examine the expression of IKKε in the specimens and cells of epithelial ovarian cancer and investigate the effect of IKKε inhibitor on cell proliferation and apoptosis. To discuss the role and clinical significance of IKKε in ovarian cancer. Method:(1) 118 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in the first Affiliated Hospital of Dalian Medical University from January 2006 to April 2013 were selected. 20 cases of patients who received the operation of hysterectomy and oophorectomy due to uterine fibroids during the same period were selected as the control. The expression of IKKε protein were detected by immunohistochemistry in normal ovarian tissues and epithelial ovarian cancer specimens and to analyze the relationship between the expression of IKKε and the clinical features of patients.(2) The protein expression of IKKε in the cell lines of OV2008(derived from endometrioid carcinoma cisplatin sensitive cell line), C13(derived from endometrioid carcinoma, cisplatin resistant cell line), A2780S(derived from undifferentiated ovarian carcinoma, cisplatin sensitive cell line), A2780CP(derived from undifferentiated ovarian carcinoma, cisplatin resistant cell line), and SKOV3(derived from human ovarian adenocarcinoma cell line) were detected by western blot after using IKKε inhibitor(0.1μM, 0.5μM) for 48 h.(3) The cellular survival and proliferation of the ovarian cancer cells were detected by MTT assay which were included OV2008, C13, A2780 S, A2780 CP, and SKOV3 that treated by different concentrations of IKKε inhibitor(0-25μM) for 48 h.(4) The rate of apoptosis of the five ovarian cancer cell lines was detected after 48 h treatment of IKKε inhibitor(0.1μM and 0.5μM). Results:(1) The immunohistochemical results showed that IKKε was highly expressed in epithelial ovarian cancer specimens with the expression rate 66.10%(78/118), compared with normal ovarian tissue with the expression rate 35.00%(3/20), which exhibited statistically significant difference(P <0.05). The expression of IKKε protein were correlated with FIGO stage, histological grade, CA125 level in preoperative serum, distribution of the tumor and patient’s survival time(P <0.05), but no correlation with age, histological type, the incidence pattern, and tumor size(P> 0.05).(2) The levels of IKKε protein in OV2008, C13, A2780 S, A2780 CP, and SKOV3 cell lines were different and the expression of IKKε decreased gradually as the increase of the concentration of IKKε inhibitor in C13, A2780 S, and A2780 CP cells for 48 h treatment.(3) Different concentration of IKKε inhibitor acting on ovarian cancer cells can inhibit the proliferation of cells in a concentration-dependent manner. As the increasing of concentration of IKKε inhibitor, its effect on the proliferation of cells gradually increased, survival rate of cells in various concentrations was decreased, compared with control group, the difference was statistically significant(P<0.05).(4) IKKε inhibitor acting on ovarian cancer cell lines for 48 h treatment can induce cell apoptosis in concentration dependent manner, The apoptosis multiples of cells increase as the increasing of the inhibitor concentration, the difference was statistically significant( P <0.05). Conclusion: The expression of IKKε protein in epithelial ovarian cancer specimens and cells was increased. IKKε inhibitor can inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner. Therefore, the result is inferred that IKKε may play an important role in the occurrence and the development of epithelial ovarian cancer, and it may serve as important therapeutic target for the patients. |
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