地钱素M抗前列腺肿瘤活性的初步探讨

Marchantin M displays growth inhibitory effects on human prostate cancer cells

目的检测苔藓植物联苄类化合物地钱素M的抗肿瘤活性,并初探其对前列腺癌细胞的作用机制。方法 MTT法检测地钱素M对人白血病细胞株(K562)、人肝癌细胞株(HepG2)、人乳腺癌细胞株(MCF-7)、人前列腺癌细胞株(LNCaP、DU145及PC-3)和人正常视网膜色素上皮细胞株(hTERT-RPE1)的增殖影响;溴脱氧尿嘧啶核苷(BrdU)掺入法检测地钱素M对PC-3细胞增殖的作用,流式细胞术检测细胞周期和凋亡的变化;Westernblot-ting检测细胞周期相关蛋白的表达;4′,6-二脒基-2-苯基吲哚(DAPI)染色法检测PC-3细胞核的变化。结果地钱素M可抑制K562、HepG2、MCF-7、LNCaP、DU145、PC-3细胞的增殖,其对PC-3细胞增殖的抑制作用尤为显著,而对hTERT-RPE1细胞增殖的抑制作用较弱。BrdU结果显示,地钱素M能够降低BrdU在PC-3细胞中的掺入;流式细胞术示,地钱素M将PC-3细胞阻滞在G0-G1期,且出现明显的subG1峰,并伴随周期相关蛋白的变化;DAPI示,细胞核发生凋亡的特征性变化。结论地钱素M具有抑制肿瘤细胞增殖的活性,并引起PC-3细胞周期阻滞,诱导细胞凋亡。

Objective To Investigate the antiproliferational effect of Marchantin M on human carcinoma cells.Methods The cytotoxic effect of Marchantin M was assessed by MTT assay.It＇s inhibitory effect on the growth of PC-3 cells was measured by incorporation of BrdU.The cell cycle progression and apoptosis of PC-3 cells were determined by flow cytometry assay.Alterations in expression of cell cycle related proteins in PC-3 cells exposed to Marchantin M were determined by Western blotting.Nucleic morphological changes of Marchantin M-treated PC-3 cells were determined by staining cells with DAPI.Results Marchantin M led to viability inhibition of K562,HepG2,MCF-7,LNCaP,DU145 and PC-3 cells in a dose-dependent manner.However,Marchantin M had no significant inhibitory effects on the growth of normal human retina pigment epithelial cells（hTERT-RPE1）.The flow cytometry assay indicated that treatment with Marchantin M resulted in cell cycle arrest at the G0/G1 phase.Further examination showed that expression of cell cycle related proteins were changed after treatment.The DAPI staining assay showed that Marchantin M treatment caused an increase in the fraction of apoptotic cells.Conclusion These observations indicate that Marchantin M is a promising compound that shows antitumor activity against prostate cancer cells.