雌马酚对映异构体影响前列腺癌PC3、DU145细胞侵袭性研究

Anti-invasion effects of R-and S-enantiomers of equol on prostate cancer PC3,DU145 cells

目的比较雌马酚对映异构体R-(+)雌马酚与S-(-)雌马酚对人前列腺癌PC3、DU145细胞侵袭性的影响,并分析相关机制。方法分别采用细胞划痕实验、侵袭实验检测癌细胞的运动能力与侵袭性的变化,采用明胶酶谱法、RT-PCR法检测相关蛋白活性和基因表达。结果 R-(+)雌马酚与S-(-)雌马酚均可显著抑制PC3、DU145细胞的运动能力及侵袭性,其中抑制PC3细胞运动能力及侵袭能力的作用较强,两种化合物比较,R-(+)雌马酚的作用更强。R-(+)雌马酚与S-(-)雌马酚还可显著抑制侵袭所必需的蛋白水解酶基质金属蛋白酶家族中MMP-2、MMP-9的活性。R-(+)雌马酚可显著增加PC3细胞ER-α的表达,对ER-β则无明显作用。结论 R-(+)雌马酚与S-(-)雌马酚可显著抑制PC3、DU145细胞运动能力及侵袭性。其中R-(+)雌马酚对PC3细胞的抗侵袭作用最强,可能由ER-α介导。

Objective To compare the effect of R-and S-enantiomers of equol on the motility and invasion in human prostate cancer cells PC3 and DU145.Methods Wound healing assay and transwell invasion assay were performed to assess the cell motility and invasion.Gelatin zymography and RT-PCR assay were performed to assess the related protein activity and mRNA expression.Result R-（＋） equol and S-（-）equol inhibited motility and invasion in PC3 and DU145 cells,separately.The results were more obvious in PC3 cells,and effect of R-（＋）equol was stronger than its enantiomer S-（-）equol.MMP-2,MMP-9,the crucial members in metastasis,were found down-regulated by R-（＋）equol and S-（-）equol.Subsequently,the estrogen receptor-α was activated by R-（＋）equol,while no such effect on estrogen receptor-β was observed.Conclusion R-（＋）equol and S-（-）equol inhibited motility and invasion in PC3 and DU145 cells,while the most strong effect was observed in PC3 cells by R-（＋）equol,which might regulated by the activation of estrogen receptor-α.