Prostate cancer, ranking as the second most common cause of cancer-related mortality, afflicts more than 90% male populations older than 65... Show moreProstate cancer, ranking as the second most common cause of cancer-related mortality, afflicts more than 90% male populations older than 65 worldwide. Conventional approach, androgen deprivation therapy, ever realized the shrinking of early-staged prostate tumors through depletion of androgens in body. However, people have gradually found that the regression is temporary, and subsequently the tumors recur and progress, which might be androgen independent. Once prostate cancer is progressed, current understanding seems to cope with prostate cancer is poorly understood. Atorvastatin (ATO) and zoledronic acid (ZOL) are both popular medications and work to control cholesterol level in blood and manage metastatic bone disease, respectively. Based on previous laboratory findings, we hypothesized that both of them might be able to play potential anti-cancer functions, and enhanced effects might be achieved by ATO+ZOL combination. Hence, we conducted experiments to characterize cellular response to ATO, ZOL, and ATO+ZOL in both AR-positive LNCaP and ARnegative PC3 prostate cancer cell lines. Besides, we studied potential mechanisms of actions of these two drugs. Our comprehensive characterization elucidates that ATO and ZOL are capable of imposing anti-cancer effects on both parental and all subclones of PC3 and LNCaP cells with different efficacies. Synergistic antiproliferative activities induced by ATO+ZOL were observed in both prostate cancer cell lines. We also found that ATO induced autophagy in PC3 cells, but not in LNCaP cells. ZOL did not induce autophagy in both cell lines. Moreover, ATO+ZOL treatment for 48h enhanced the induction of autophagic activity in comparison with ATO treated PC3 cells. Notably, preliminary pathway analysis based on microarray data demonstrates that in LNCaP cells, 7 KEGG pathways were affected by ATO whereas in PC3 cells ATO altered 47 KEGG pathways. These data suggested that ATO may be particularly active in AR- negative prostate cancer. These observations offer novel insights for understanding roles of ATO, ZOL and ATO+ZOL in LNCaP and PC3 cells. ATO and ATO+ZOL might provide benefits for prostate cancer patients and our results provide some evidences for further investigation of these two drugs for potential clinical application. M.S. in Biology, May 2012 Show less
