Research Of Arsenic Trioxide Induced Prostate Cancer Cells PC–3Apoptosis JNK Signal Transduction Pathways

Objective The incidence of prostate cancer in China is increasing rapidly andhas become common urology diseases, but for the treatment of androgenindependence prostate cancer is no effective treatment clinically。Arsenic trioxide isarsenic in traditional medicine extract, its use in acute promyelocytic leukemia andthe clinical effect on primary liver cancer, have been recognized academic circles，Studies have shown that arsenic trioxide （As₂O₃） can induce androgen-independentprostate cancer （HRPCa） cell line PC-3cell apoptosis, but the mechanism is unclear.Mitogen-activated protein kinase （MAPK） signaling pathway is a widespread in theanimal cell signaling pathway, is also more widely studied in recent years in theprocess of tumor cell apoptosis signaling pathway. JNK signaling pathways is one ofthe most important pathways in MAPK signaling pathways, and plays an importantrole in the process of the apoptosis of tumor cells, This study investigated the JNKsignaling pathway in As₂O₃induced prostate cancer PC-3cell lines during apoptosis.Methods: Androgen independent prostate cancer cells PC-3was treated withdifferent concentrations of As₂O₃. MTT （Methyl Thiazolyl Tetrazolium blue） assaydetected the cell growth inhibition after24,48,72h; Application of EdU cellsproliferation concentration detection method to detect different As₂O₃PC-3cellproliferation after24h, The expression of p-JNK1/2by Western blot, and Annexin V,PI double staining method was used to examine the apoptosis rate before and afterJNK signal was blocked by SP600125which is a JNK inhibitor.Results:AS2O3inhibited the growth of PC-3cells in a concentration-and-timedependent manner. Significant difference among groups （P <0.05）, Application ofEDU cells proliferation concentration detection method to detect different As₂O₃PC-3cell proliferation after24h, We found that the PC-3cell proliferation graduallyreduced with the increase of drug cconcentration, Western Blot analysis showed that non-phosphorylated JNK protein expression was no difference （P>0.05）, andphosphorylation of JNK1/2expression increased （P <0.05）, As₂O₃can quicklyactivate the JNK protein phosphorylation expression, which plays a biologicalactivities. In different concentrations AS2O3（2,10,20μmol/L） after24hours, PC-3apoptosis rate were18.9%±0.43%;24.8%±0.3%;49.7%±1.8%, respectively. PC-3cell apoptosis rates were reduced to11.8%±0.97%;21.7%±0.43%;38.2%±1.13%after joined highly selective inhibitors of the JNK pathway SP600125. Inhibition ofJNK pathway can significantly reduce AS2O3induced apoptosis in PC-3cells（P<0.05）.Conclusion: As₂O₃induced prostate cancer PC-3cells apoptosis through theactivation JNK signaling pathways which played an important role in As₂O₃inducedandrogen independent prostate cancer PC-3cell apoptosis.