Contrasting effects of aspirin on prostate cancer cells: Suppression of proliferation and induction of drug resistance

BACKGROUND. Aspirin is widely used as a preventive measure against occlusiv e vascular diseases. Since the age group in which aspirin use has become pr evalent is similar to the one presenting with prostate cancer, we decided t o examine the potential effects of aspirin on prostate cancer. METHODS. We studied the effects of plasma-attainable concentrations of aspi rin (0.5-2 mM) on the human prostate cancer cell Lines LNCaP, PC-3, and DU 145, employing cytotoxicity assays and flow cytometric analyses. RESULTS. Incubation with aspirin for 3 days reduced cellular proliferation by up to 35-55% in each cell line studied, but induced a tripling of the pe rcentage of cells expressing glycoprotein (an efflux pump conferring multid rug resistance) only in the LNCaP cells. Both effects were dose-dependent. The effect on P-glycoprotein expression was reflected in the induction of r esistance against adriamycin cytotoxicity. Furthermore, this protective eff ect of aspirin was reversed by a specific P-glycoprotein inhibitor, PSC833. The cellular expression of P-glycoprotein returned to normal within 3 days following the removal of aspirin. Aspirin did not affect the cell cycle di stribution of LNCaP cells. CONCLUSIONS. This study suggests that aspirin enhances the ability of andro gen-responsive prostate cancer cells to resist chemotherapeutic drugs. Thes e findings could potentially have significant clinical ramifications for pr ostate cancer patients taking aspirin shortly before or during chemotherape utic sessions.