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The Initial Observation That AR Inhibits Prostate Cancer Cell Necrosis

Posted on:2013-11-13Degree:MasterType:Thesis
Country:ChinaCandidate:Z H LiuFull Text:PDF
GTID:2334330485452839Subject:Surgery Urology outside
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Objective:Androgen receptors(androgen receptor,AR)is the intracellular ligand-dependen t trans-transcriptional regulatory protein,belongs to the nuclear receptor famil-y.Androgen receptor signaling pathway in prostate cancer development and invasion plays an important role in the mechanism of its regulating prostate cancer cell surv-al and apoptosis.Cell necrosis is a form of cell death,apoptosis and necrosis were w significantly different on the mechanism and morphology.The results show that occurrence and course of cell necrosis can control to a certain extent,and under certain conditions,apoptosis can transform into necrosis.In this study,we use RNA interference technology to reduce the level of AR expression in prostate cancer cells,respectively,using the water bath method and the hydrogenperoxide-induced prostate cancer cell necrosis,to explore the impact of AR on prostate cancer cell necrosis,and further research on AR regulation of cell necrosis mechanism.Methods:1.We use water bath heating and hydrogen peroxide to induce prostate cancer cells to necrosis,and build the necrosis model.2.We used RNA interference technology to konckdown the expression of AR in huamn prostate cancer and the expression of AR was detected by Western blotting.3.We use water bath heating and hydrogen peroxide to induce C4-2,siAR/C4-2 and PC-3 PC-AR9 cells to necrosis.4.We use water bath heating and hydrogen peroxide to induce C4-2,siAR/C4-2 and PC-3 PC-AR9 cells adding 10nM DHT to necrosis.5.Flow cytometry anaylisis was used to detect the cell necrosis rate..6.The NF-κB change before and after necrosis was detected by Western blotting.Results:1.We use RNA transfection of human prostate cancer C4-2 cells,and screene AR protein expression level decreased by about 80%of monoclonal cells.2.With the extension of the water bath time,or hydrogen peroxide,cell necrosis rat increased accordingly.3.After AR protein expression level decreased prostate cancer siAR/C4-2 cell necrosis rate was significantly higher(P<0.05).4.AR expression-positive prostate cancer cells PC-AR9 cell necrosis rate was significantly lower(P<0.05).5.Western blotting detected no statistically significant expression levels of NF-κB before and after the C4-2 cell necrosis.Conclusions:1.AR protein in prostate cancer cells can inhibit the necrosis using water bath heating and hydrogen peroxide-induced.2.Androgen receptor signaling pathway in the regulation of cell necrosis could be achieved through the activation of NF-κB signaling pathway.
Keywords/Search Tags:prostate cancer, androgen receptor, cell necrosis
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