类黄酮衍生物DMF诱导人前列腺癌PC3细胞凋亡的实验研究

DMF induces apoptosis in human androgen-independent prostate cancer PC3 cells in vitro

目的:检测3-(2-氯苯基)-1-(2-羟基-4,6-二甲氧基-3-((-N,N-甲基乙基胺)甲基)苯基)-丙-2-烯-1-酮(DMF)对人前列腺癌PC3细胞的抗肿瘤活性,并对相关作用机制进行研究。方法:采用MTT法测定DMF对PC3细胞增殖的体外抑制作用;流式细胞术检测PC3细胞凋亡率;JC-1染色观察线粒体ΔΨm变化;Western blot法检测凋亡相关蛋白表达。结果:DMF对PC3细胞具有显著的抗增殖作用。流式细胞术结果表明,这种抗增殖作用是通过诱导细胞凋亡实现的。DMF可诱导PC3细胞的线粒体膜电位(ΔΨm)下降,并呈明显的时间和剂量依赖效应。Western blot结果显示,DMF促进PC3细胞内procaspase-3活化及其下游底物PARP降解。同时,DMF还促进Bax蛋白表达上调和Bcl-2蛋白表达下调,使Bax/Bcl-2比值明显增加。此外,DMF可抑制PC3细胞内p38蛋白的磷酸化。结论:DMF可显著抑制PC3细胞增殖,其促凋亡作用可能是通过线粒体信号转导途径实现的。

Objective： To evaluate the antiproliferative activity of 3-（2-chlorophenyl）-1-（2- hydroxy-4, 6-dimethoxy-3-（（ethyl （methyl） amino ） methyl ） phenyl ） prop-2-en-1-one （DMF） against human androgen-independent prostate cancer PC3 cells in vitro and its underlying mechanisms. Methods： The cytotoxic effect of DMF on PC3 cells was measured by MTT assay. Induction of apoptosis was assessed by propidium iodide staining and flow cytometric analysis. Changes of mitochondrial membrane potential （△ψm） were detected by JC-1 staining. The levels of apoptosis related proteins were analyzed by Western blot. Results： DMF exhibited high efficiency on cell growth inhibition in PC3 cells with an IC50 value of （9. 5±0. 2）μmol/L. Flow cytometric analysis indicated that DMF could induce apoptosis in PC3 cells. A significant decrease of mitochondrial membrane potential was observed in PC3 cells treated with DMF,which was in a time-and dose-dependent manner. The results of Western blot indicated that DMF induced the activation of caspase-3, increased the ratio of Bax/Bcl-2 and downregulated the expression of phosphate-p38. Conclusion ： DMF is a potential compound against PC3 cells and the mitochondrial pathway might be involved in DMF-induced apoptosis in PC3 cells.