Effects Of Dihydroartemisinin On Modulating UCHL1Expression In Human Prostate Cancer Cell Line PC-3and Its Mechanism

Objective: To research the effects and mechanism ofdihydroartemisinin on modulating UCHL1gene expression in humanprostate cancer cell line PC-3and its mechanism.Methods: PC-3was selected and were devided into three groupsduring the culture course in vitro.They were contral group，dihydroartemisinin groups(12.5μmol/L、25μmol/L、50μmol/L、100μmol/L)， Cells in the positive control group were cultured in the mediawith5-Aza-2’-deoxycytidine at2.5μmol/L.CpG island of ubiquitincarboxyl-terminal hydrolase L1(UCHL1) methylation levels weredetermined by Bisulfite sequencing PCR(BSP).UCHL1mRNA expressionlevels were determined via realtime fluores-cence quantitative PCR，whereas the expression of UCHL1protein were determined using WesternBlot technique.Results: DHA can induce prostate cancer PC-3cells to undergoapoptosis, and a certain degree of dose-dependent manner, with the doseincreasing concentrations of pro-apoptotic effect is more obvious.In the dihydroartemisinin group（25μmol/L），UCHL1promoter methylation levelsdecreased dramatically（P＜0.01）; The mRNA expression of UCHL1dramatically increased（P＜0.01）.The protein expression of UCHL1significantly increased（P＜0.01）. Mechanism may be related that DHAreduced the mRNA expression of DNA methyltransferase increased（P＜0.01）.Conclusion: Dihydroartemisinin can reverse the methylation ofUCHL1CpG island，the mechanism may be increase the mRNA expressionof DNA methyltransferase.