Silence Of STAT3Signaling Pathways Potentiate Chemotherapy Of Human Ovarian Carcinoma Cell Lines To DDP And The Preliminary Research About The Molecular Mechanism

【Objective】 Ovarian carcinoma is the leading cause of gynecologic cancer deathsamong women, paclitaxel and cisplatin-centered chemotherapy is the first linetreatment for human ovarian cancer. However, chemoresistance remains a majorobstacle to successful treatment. Recent evidence indicated that signal transducer andactivator of transcription-3(STAT3) is a determinant of chemoresistance; it wasrelated to tumor recurrence in a large number of solid malignancies. In this study, weexplore the reversion of chemoresistance in human ovarian carcinoma cell lines bysilencing STAT3signaling pathways.【Methods】SiRNA targeting STAT3was transfected into ovarian carcinoma cells,the mRNA and protein expression of STAT3and phosphorylated STAT3weredetermined by Real time PCR and Western blotting, respectively. The apoptosis ratewas measured by flow cytometry (FCS). The cell viability was detected by MTTassay.【Results】Compared with the control group, STAT3and p-STAT3expression in thecells treated with STAT3siRNA were significantly blocked. At the same time, theapoptotic rate was significantly increased and the IC50of DDP was also significantlydecreased.【Conclusion】Silence of STAT3signaling pathways can potentiate sensitivity ofhuman ovarian carcinoma cell lines to DDP. 【Objective】The preceding research have confirmed that silencing STAT3couldstrengthen chemotherapy of human ovarian carcinoma cell lines to DDP. In thefollowing research, we mainly continue to explore the molecular mechanisms aboutthe relationship between STAT3and the drug resistance of ovarian cancer cells.【Methods】Western blotting and flow cytometry were used to detect the expressionof STAT3and p-STAT3in protein levels and the changes of sensibility of ovariancancer cell line to DDP, when DDP-sensitive ovarian cancer cell line was inducedby exogenous IL-6. Using TMRE (Tetramethylrhodamine ethylester) staining methodto detect the mitochondrial membrane potential (ΔΨm) of different ovarian carcinomacell groups. Bcl-2、 Bcl-xl、 Bax and Cytochrome C which are related inmitochondrial-related apoptosis were tested by Western blotting. Immune-fluorescence and Western blotting were used to inspect the expression of LC3whichis related to autophagy, when the DDP-resistant ovarian carcinoma cells were exposedto DDP. At the same time combined with3-MA(3-methyladenine), the cell apoptosis rate and expression of p-STAT3were tested by flow cytometry and western blotting.【Results】IL-6induced the activation of STAT3in DDP-sensitive ovarian cancercells, reduced the sensitivity of those cells to DDP, but this effect was conversed byblocking STAT3. We also found that combining DDP and siRNA targeting STAT3resulted in the collapse of mitochondrial membrane potentials as well as the inductionof mitochondrial-related apoptosis. Exposed to DDP the DDP-resistant ovariancarcinoma cells could induce the happening of cell autophagy and the cell apoptosisrate. However,3-MA could block this process, restore the sensitivity of ovariancarcinoma cells to DDP and inhibit the STAT3activation. Targeting silence the STAT3signaling pathways did not attenuate LC3Ⅱ accumulation and regulate the autophagy.【Conclusion】Targeting silence the STAT3signaling pathways could reverse thechemoresistant IL-6induced, enhanced the mitochondrial-related apoptosis, play aimportant role in autophgy. These effects may enabled silencing STAT3signalingpathways reverse the chemoresistance of human ovarian carcinoma cell line.