丹参酮ⅡA增强顺铂抗前列腺癌作用及分子机制研究

Synergistic antitumor effects of tanshinone ⅡA in combination with cisplatin via apoptosis in the prostate cancer cells

探讨丹参酮ⅡA增强顺铂抗前列腺癌作用及其分子机制。采用MTT法检测细胞增殖,流式细胞仪检测细胞周期变化及凋亡率,Western blotting检测蛋白的表达水平,高效液相色谱法检测细胞内顺铂含量。结果表明:丹参酮ⅡA通过增加细胞内顺铂浓度从而产生协同抗细胞增殖作用,两者联用可诱导LNCaP及PC3细胞周期阻滞于S期并引起细胞凋亡,caspase及Bcl-2家族成员均参与了该凋亡过程。提示丹参酮ⅡA能明显增强顺铂的抗前列腺癌作用,并对激素依赖性和非依赖性前列腺癌均有效。

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP ceils with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.