| Objective:At the tissue level, we tested the expression of beclinl, a regulatory gene of autophagy, Survivin and ERCC1,drug-resistant related gene, in benign ovarian tumor tissue,borderline ovarian tumor tissue and epithelial ovarian cancer. And analysising the expression of beclinl, Survivin, ERCC1 in different tumor tissues, or different pathological characteristics, even in platinum sensitive patients and platinum Resistance patients. The aim of the present study is to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Hoping to improve the effect of epithelial ovarian cancer chemotherapy, and to provide theoretical basis for the prognosis of ovarian cancer.At the individual level, through establishing the model of SKOV3/DDP cells in nude mice, we investigated the feasibility of autophagy inhibitor hydroxychloroquine combined cisplatin in the treatment of drug-resistant human ovarian carcinoma. From the angle of cell autophagy, analyzing the effect of HCQ in the chemotherapy of ovarian cancer. Exploring the relationship between cell autophagy and ovarian cancer, autophagy and the chemotherapy drug resistance. Hoping to improve ovarian cancer treatment status and provide new thought from a relatively new angle.Methods:1. Expression of Beclinl, survivin and ERCC1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC),13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue.2. Forty BALB/C (nu/nu) mice with implanted tumor of SKOV3/DDP cells were randomly divided into 4 groups(n:4), including the control group, HCQ group, DDP group, HCQ plus DDP group. Adopting the method of intraperitoneal injection to treatment these nude mices. In the control group, nude mices were given 0.2ml normal saline, 1time per 2d. In the HCQ group, nude mices were given 0.2ml HCQ,5mg/kg, 1time per 2d. In the DDP group, nude mices were given 0.2ml DDP,3mg/kg, ltime per 2d. And in the HCQ plus DDP group, nude mices were given 0.2ml HCQ plus DDP, HCQ,5mg/kg, DDP,3mg/kg,1 time per 2d. Before and after our treatment,we observed and recorded the 4 groups nude mices’body weight and tumor volume.3. With SPSS 19.0 software dealing with our experimental datas, using chi-square test, t test, Fisher’s exact test to evaluate the probability method. For all p values, p < 0.05 was considered statistically significant.Results:1. In the method of Immunohistochemical staining, beclinl was mainly stained in cytoplasm with high intensity dyeing.2. In the method of Immunohistochemical staining, ERCC1 was stained in caryon with low intensity dyeing.3. In the method of Immunohistochemical staining, beclinl was mainly stained in cytoplasm with low intensity dyeing.4. The positive expression of beclinl in benign epithelial ovarian tumor tissue (BET), borderline ovarian tumor tissue, epithelial ovarian cancer (EOC) was 15.4%, 50.0%,56.4%. Beclinl expression was significantly higher in the EOC than the BET (p<0.05).5. The positive expression of ERCC1 in benign epithelial ovarian tumor tissue (BET), borderline ovarian tumor tissue, epithelial ovarian cancer (EOC) was7.7%, 50.0%,15.4%. ERCC1 expression was significantly higher in the borderline ovarian tumor tissue than the BET and the EOC (p<0.05).6. The positive expression of beclinl in Ⅰ-Ⅱ stage and Ⅲ-Ⅳ stage was 36.8%, 75.0%. The expression of Beclinl significantly correlated with FIGO stage (p<0.05).7. The positive expression of survivin inⅠ-Ⅱ stage and Ⅲ-Ⅳ stage was 5.3%, 35.0%. The expression of survivin significantly correlated with FIGO stage (p<0.05).8. The positive expression of beclinl in platinum-sensitive EOC patients and platinum-resistant patients was 15.4%,53.8%. For platinum-sensitive EOC patients, positive expression of Beclinl was lower than in platinum-resistant patients (p<0.05).9. SKOV3/DDP cells had irregular cell torm with monolayer growth. And SKOV3/DDP cells growed slowly. Cells passage culture needed 6 even 7 days.10. Forty BALB/C (nu/nu) mice needed 28 days to form the implanted tumor of SKOV3/DDP cells.11. Before and after the treatment,4 groups of nude mices’body weight all had decrease. Body weight in the control group and the control group decreased significantly (p<0.05).12. In the control group, HCQ group, the DDP group and HCQ plus DDP group, specific value of final weight (FBW) and initial weight (IBM) was higher than 0.8.13. The control group had the largest tumor volume than HCQ group, DDP group, and HCQ plus DDP group.14. The control group had the largest tumor weight(0.78g). Tumor weight in HCQ group, DDP group, and HCQ plus DDP group was 0.59g,0.55g,0.16g.15. The inhibitory rate in the HCQ group, the DDP group and HCQ plus DDP group was 19.5%,27.1%,68.4%oConclusions:1. Beclinl may be involved in the occurrence of epithelial ovarian cancer.2. Beclinl may be implicated in development of epithelial ovarian cancer.3. Survivin may be implicated in development of epithelial ovarian cancer.4. ERCC1 might be a potential predictive marker for neoadjuvant treatment in early stage of ovarian cancer.5. Inhibition of expression of beclinl may suppress autophagy to enhance the efficiency of platinum-sensitive ovarian cancer.6. Under the condition of in vitro culture, SKOV3/DDP cells grow slowly.7. The rate of tumor formation is 100%.8. HCQ plus DDP group has the greatest tumor suppression effect. HCQ may enhance the efficiency of platinum-sensitive ovarian cancer. HCQ and DDP may have the synergy of antitumor.9. Combining HCQ with DDP may reduce the side effects of DDP. In clinical chemotherapy may through the combination to reduce the toxicity of DDP, improving the patient’s tolerance.10. At the initial period of tumor development, tumor cells get protection from cell autophagy. |
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