Study About The Expression Of NF-κB In Human Epithelial Ovarian Carcinoma And Its Resistance To Apoptosis Induced By Carboplatin

Ovarian carcinoma is one of the commonest malignant gynecological tumors. Approximately 70% of women are diagnosed in an advanced stage due to unclear symptom and lack of effective early diagnostic methods. So the five-year survival rate of ovarian cancer patients is still low, about 30%. Chemotherapy is very important in the treatment of ovarian cancer in that its effect directly decides the prognosis of patients. At present there has been an agreement that the induction of apoptosis by chemotherapeutic drugs is the main mechanism through which tumor cells are killed and the inhibition of apoptosis may cause the resistance of tumor cells to chemotherapy. Apoptosis is an active cell death under the control of the apoptosis-related genes. The products of genes, which suppress the undergoing apoptosis, play an important role in the resistance of tumor cells to chemotherapy. NF- k B is a factor which can antagonize cell apoptosis. It has been demonstrated that some apoptosis-inducing factors elicit tumor cells committing suicide, and at the same time they also stimulate NF- k B ,which will start the transcription of some certain genes .The products of these genes may hamper the signaling pathway, which will lead to the apoptosis of cells. In recent studies, it hasbeen indicated that some anti-tumor drugs can activate NF- k. B, which may decrease their activity in inducing apoptosis as they induce the apoptosis of tumor cells. So, it is a meaning reseach on exploring the role of NF- k B in the generation of epithelial ovarian neoplasm and the effect on chemotherapy.OBJECTIVES: The present study intends to explore the role of NF- k Bin the generation and progression of epithelial ovarian neoplasm and the correlation between the NF- k. B expression levels and the clinical pathologic stages by examining the expression of NF- k B in the human epithelial ovarian neoplasm tissues and ovarian cancer cell lines. It also aims at investigating the role that NF- k B and its specific inhibitor (PDTC) play in the ovarian cancer cells apoptosis induced by carboplatin and exploring the mechanism of ovarian cancer cells' resistance to apoptosis induced by chemotherapy drugs so as to provide an experimental foundation for a highly-efficient chemotherapeutic drug.METHODS: 1) Immunohistochemical staining (SABC) was used to detectthe expression of NF- k B in the 104 cases of the ovarian epithelial neoplasm tissues and in 4 kinds of ovarian carcinoma cell lines. The transferring of NF-k B from the cytoplasm to the nucleus was observed by the immunohistochemical SABC method. 2) Electrophoretic mobility shift assay (EMSA) was performed to examine the NF- k B activity in the nucleus treated with carboplatin or carboplatin combined with PDTC. 3) MTT assay and flow cytometry were used to analyze the death rate and apoptosis rate in different conditions. 4) RT-PCR was used to detect the expression level of survivin mRNA in different conditions.RESULTS: 1) The positive rates of NF- k B expression in the benign,...