Abstract：
Ginsenoside 20 (R)-25-methoxy-dammarane-3 β, twelve β, 20 triol (AD-1) is a promising new drug for the treatment of prostate cancer, but its bioavailability is low. This study investigated the effects of the main metabolites PD and M6 of AD-1 on prostate cancer cell PC3. The in vitro experimental results showed that the IC50 values of PC3 cells treated with PD and M6 were 65.61 and 11.72, respectively. Both PD and M6 inhibited the migration of PC3 cells, and the cell cycle was blocked in the G1 phase. The apoptosis rates of cells following M6 treatment at concentrations of 7.5, 15, and 30 μM were 13.4 %, 17.5 %, and 41.4 %, respectively, which stimulated the expression of apoptosis protein and significantly increased intracellular ROS levels. In xenograft models, PD and M6 have been reported to significantly inhibit tumor growth. We used a genome-wide mRNA expression profile to study the effects of PD and M6 on gene expression in PC3 cancer cells. PD and M6 induced downregulation of HSP70 subtypes HSPA1A and HSPA1B. RT-PCR confirmed that the significant down-regulation of HSP70 subtype expressions was consistent with the results of Transcriptome analysis. Moreover, M6 significantly downregulated the expression of AR, which was further proved by Western blot analysis. In summary, our research findings provide a scientific basis for interpreting the significant activity of AD-1 in prostate cancer, and for the research and development of PD and M6 as novel HSP70 inhibitors.
摘要：
人参皂苷20(R)-25-甲氧基-达玛烷-3β，十二β，20三醇(AD-1)是一种很有前途的治疗前列腺癌的新药,但是它的生物利用度很低。这项研究调查了AD-1的主要代谢物PD和M6对前列腺癌细胞PC3的影响。体外实验结果表明，用PD和M6处理的PC3细胞的IC50值分别为65.61和11.72。PD和M6均抑制PC3细胞的迁移，细胞周期在G1期被阻断。在浓度为7.5、15和30μM的M6处理后，细胞的凋亡率为13.4％，17.5%,和41.4%，分别,刺激细胞凋亡蛋白的表达,显著增加细胞内ROS水平。在异种移植模型中,已经报道PD和M6显著抑制肿瘤生长。我们使用全基因组mRNA表达谱来研究PD和M6对PC3癌细胞中基因表达的影响。PD和M6诱导HSP70亚型HSPA1A和HSPA1B的下调。RT-PCR证实HSP70亚型表达的显著下调与转录组分析的结果一致。此外，M6显著下调AR的表达，Westernblot分析进一步证明。总之,我们的研究结果为解释AD-1在前列腺癌中的重要活性提供了科学依据，并用于PD和M6作为新型HSP70抑制剂的研发。
