PACLITAXEL, BROPIRIMINE AND LINOMIDE - EFFECT ON GROWTH-INHIBITION INA MURINE PROSTATE-CANCER MODEL BY DIFFERENT GROWTH-REGULATORY MECHANISMS

Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate cancer model. All drugs were effective in impeding tumor gro wth but the mechanisms of action varied. Paclitaxel inhibited bcl-2 ex pression suggesting an apoptotic mechanism. Bropirimine, while inhibit ing bcl-2 expression also significantly depressed tumor necrosis facto r-alpha (TNF-alpha) expression. In the bropirimine treated group there was also a correlation between angiogenesis and cyclin D expression. Finally, linomide significantly decreased angiogenesis. Since the mech anism of action of these drugs differ, combining them at lower doses m ight maintain therapeutic efficacy while reducing toxicity. (C) 1998 P rous Science. All right reserved.