P28-9 Paclitaxel suppresses c-myc signaling pathway to induce apoptosis in PC9 cells

Paclitaxel is used as a first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, breast cancer. Paclitaxel induced cell death requires a cell death pathway, but the specific factors and precise mechanisms are not well known. In this study, paclitaxel was tested in vitro for the molecular mechanism of its anti-cancer activity in human PC9 cells. PC9 cells were treated with paclitaxel and then evaluated with flow cytometry and western blot analysis. Paclitaxel induced G1 phase arrest of the cell cycle via down-regulation of several related cell cycle regulators, including CDC25A, cyclin D1, and cyclin E1. Paclitaxel also caused a profound decrease in RB phosphorylation, leading to an elevated association between RB and E2F1 and the consequent suppression of E2F1 activity. The protein level of c-myc, which can activate the expression of many downstream cell cycle regulators, was dramatically inhibited by paclitaxel. Additionally, paclitaxel-induced DNA damage resulted in the deregulation of the p14ARF/Mdm2/p53 pathway, disrupting cell proliferation. Consequently, paclitaxel caused mitochondrial damage and ultimate apoptosis in human PC9 cells. In light of these results, paclitaxel has considerable therapeutic potential against PC9 cells.