Expression And Significance Of IFITM1 In Epithelial Ovarian Carcinoma

BACKGROUNG Over the past few decades, Ovarian cancer’s deathrate remains the highest in gynecological malignancies, while its 5-year survival rate still the lowest. More than 70% of the patients are diagnosed at advanced stage, The cytoreductive surgery combined with platinum-based chemotherapy is the standard operation in ovarian cancer, however, drug resistance will happy to 85-90% of the patients. Actually, the average recurrence time was only 18 months, with 50% of the clinical remission and 30% of the pathological even though we use the most satisfied treatment and chemotherapy. Therefore, It’s a tough proposition of the specific early-diagnostic tools and drug-resistant reversal. Simultaneously,to explore representative tumor biological molecular target is particular urgent. Interferon-induced transmembrane protein 1 is one of the members of the family of interferon-induced transmembrane protein, its gene product ia the parameter of lymph cell and one of the white cell antigens. The levels of IFITM1 can be raised or depressed in different tumors, such as the mechanism. For the past few years, many studies have confirmed that the high levels of IFITM1 are discovered in colon carcinoma, lung cancer, rectum cancer, gastric cancer, and head and neck aquamous cell carcinoma. Its effect in cancer development, invasion,chemotherapy sensitivity attracts wide attention worldwide.The oversea experiments have indicate that the IFITM1 is a promising gene, our internal research has not carrying out yet. In this study, The expression level of IFITM1 was detected by the Western blot analysis in different ovaries, and the immunohistochemical method(SP) was used to determine the expression levels of IFITM1 among normal ovarian tissue cases, benign ovarian tumor cases, borderline ovarian tumor cases and ovarian carcinoma cases. Then the relationship between the expression level of IFITM1 in ovarian carcinoma and the clinicopathological features was analyzed by statistics. The immunohistochemical method(SP) was used to determine the expression levels of IFITM1 among the human ovarian carcinoma A2780 cell line and the cisplatin-resistant cell line CP70. The expression level of IFITM1 was detected by the Western blotting, real-time PCR, MTT, FCM analysis in the cell lines A2780/CP70. This research is to investigate the role of IFITM1 in the carcinogenesis, to evaluate the relationship between expression of IFITM1 and the drug-resistance of platinum-based chemotherapy in human ovarian carcinoma, to provide better evidence to the further study of IFITM1 in diagnosis and targeted treatment of ovarian carcinoma. OBJECTIVES 1. To investigate the role of Interferon-induced transmembrane protein 1(IFITM1) in the carcinogenesis and evaluate its clinical significance in epithelial ovarian carcinoma. 2. To investigate the relationship between expression of Interferon-induced transmembrane protein 1(IFITM1) and the drug-resistance of platinum-based chemotherapy in human ovarian carcinoma. 3. To observe the effect of IFITM1 si RNA on the sensitivity to cisplatin in ovarian cancer cells, and to provide some evidences that IFITM1 is a molecula r target to reverse cisplain resistance in ovarian cancer. METHODA AND CONTENT 1. The expression level of IFITM1 was detected by the Western blot analysis in different ovaries, and the immunohistochemical method(SP) was used to determine the expression levels of IFITM1 among normal ovarian tissue cases, benign ovarian tumor cases, borderline ovarian tumor cases and ovarian carcinoma cases. Then the relationship between the expression level of IFITM1 in ovarian carcinoma and the clinicopathological features was analyzed by statistics. 2. The immunocytochemistry and the Western blotting analysis were used to determine the expression levels of IFITM1 in the human ovarian carcinoma A2780 cell line and the cisplatin-resistant cell line CP70. 3. The object was the cisplatin-pretreated cell lines A2780/CP70. the expression level of IFITM1 was detected by the Western blotting analysis, Real-time PCR and MTT in the cell lines A2780/CP70. 4. Real time PCR and Western blot were used to determine IFITM1 expression respectively in CP70 cells transfected with si RNA. MTT and FCM assays were performed to evaluate the influence of IFITM1 gene silence on cisplain sensitivity of CP70 cells. RESULTS 1. The immunohistochemical technique showed that the positive rate of IFITM1 expression in ovarian carcinoma was higher than that of ovarian, benign ovarian tumor and borderline ovarian tumor with a dramatical statistic significance. The expression level of IFITM1 was correlated with pathology type, tumor grad and FIGO stage(advanced stage 79.1 %, early stage 73.9 %) in ovrian carcinoma. The expression intensity of IFITM1 protein in ovarian carcinoma was significantly related to its chemotherapy sensitivity. 2. The immunocytochemistry display that IFITM1 was mainly licated in the cytolemma of A2780/CP70 cell lines. Western blot analysis showed that IFITM1 expression in the CP70 cell lines was increased compared with A2780 cell lines. 3. The Western blot and Real-time PCR analysis showed that IFITM1 expression in the cisplatin-pretreated cell lines A2780/CP70 cell lines was increased by cisplatin. 4. CP70 cells transfected with IFITM1 si RNA diaplayed an decreased expression of IFITM1 The sensitivity to cisplain is enhanced. CONCLUSIONS 1. The expression levels of IFITM1 were gradually i ncreased in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumor and ovarian carcinoma. Positive expression level of IFITM1 played a vital role in carcinogenesis and progression of ovarian carcinoma. Our research can provide better evidenc e to the further study of IFITM1 in diagnosis and targeted treatment of ovarian carcinoma. 2. IFITM1 expression in the cisplatin-pretreated cell lines A2780/CP70 cell lines was increased by cisplatin. IFITM1 played a vital role in the drug-resistance to platinum-based chemotherapy of human ovarian carcinoma. Our research can provide better evidence to the suggestive effect of IFITM1 in trestment of ovarian carcinoma. 3. Knockdown of IFITM1 inhibited cisplatin resistance in CP70 cells. IFITM1 is a potential therapeutic target for human ovarian cancer. This suggests that IFITM1 plays an important role in cisplatin resistance of ovarian cancer cells.