Proteasome inhibitor 1 enhances paclitaxel-induced apoptosis in human lungadenocarcinoma cell line

Paclitaxel is a chemotherapeutic drug that induces apoptosis in turner cell s by stabilizing microtubules, prevents normal mitosis, and blocks the cell cycle at the G2/M phase. We have previously reported that the activation o f caspase-3 and caspase-8 plays a crucial role in paclitaxel-induced apopto sis. Anti-tumor reagents including paclitaxel, irradiation, and other stimu li activate the transcription factor NF-kappaB, which has the ability to su ppress the apoptotic potential of those stimuli. Using a human lung adenoca rcinoma cell line (LC-2-AD), we therefore examined whether the inhibition o f NF-kappaB activity by proteasome inhibitor 1 (PS1) could become a new adj uvant therapy for cancer. A synergistic effect on apoptosis induction was o bserved with the combination of more than 0.1 mug/ml paclitaxel and 0.5 muM PS1. An increase in the cell number of apoptotic cells is correlated with the Loss of Delta phim and the activation of caspase-3 and caspase-8. Furth ermore, augmented apoptosis is related to NF-kappaB activation. Based on th ese findings, we propose that the combination of paclitaxel with PS1 could be a new strategy for cancer treatment.