Medulative effect of dihydroartemisinin on UCHL1 gene expression in human prostate cancer PC-3 cells and its mechanism / 肿瘤

ABSTRACT

Objective: To investigate the effect of dihydroartemisinin (DHA) on expression of tumor suppressor gene ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in human prostate cancer cell line PC-3, and explore its regulative mechanism. Methods: PC-3 cells were treated with different concentrations (25, 50, and 100 μmol/L) of DHA for 48 h, while PC-3 cells without DHA treatment were used as the control. Then the apoptosis and cell cycle distribution were detected by flow cytometry. The expressions and cellular locations of DNA methyltransferase 1 (DNMT1) and UCHL1 proteins were detected by immunofluorescence staining. The expression levels of UCHL1, DNMT1, phospho-Akt (p-Akt) and Akt proteins were detected by Western blotting. The 1 μmol/L phosphoinositide-3-kinase (PI3K) inhibitor Wortmanin was used as a positive control to analyze the expression of p-Akt protein in DHA-treated group. Results: DHA significantly induced the apoptosis of PC-3 cells and arrested the cell cycle distribution at phase G2/M as compared with those of the control group (both P 0.05) in the DHA-treated group and the positive control group. The downregulation of p-Akt expression was more obvious in high-concentration of DHA-treated group, much closer to that in the positive control group. Conclusion: DHA can inhibit the expression of DNMT1, restore the function of UCHL1 gene, induce the apoptosis of PC-3 cells, and block the cell cycle progression. These mechanisms may be related to the suppressive activity of PI3K/Akt pathway.