PD98059 enhancing the effects of oxaliplatin on colorectal cancer cells mediated by PUMA expression / 第三军医大学学报

ABSTRACT

Objective To investigate the effects of MEK1 specific inhibitor PD98059 on oxaliplatin-treated colorectal cancer cells and the potential mechanism. Methods Cell proliferation was assessed by MTT assay after transfecting MEK1 active plasmid into LoVo cells. LoVo cells were treated with oxaliplatin or PD98059, and the proliferation was assessed by MTT assay. PUMA expression and ERK activity were determined by Western blot. Apoptosis was assessed by Hoechst 33258 dye after PUMA expression was suppressed. Results Increasing activity of ERK enhanced the proliferation of LoVo cells. The activity of ERK was suppressed by oxaliplatin. PD98059 and oxaliplatin decreased the proliferation rate of LoVo cells synergistically. PUMA expression increased after PD98059 and oxaliplatin treatment. The suppression of PUMA expression by stably transfecting PUMA anti-sense vector decreased apoptosis induced by oxaliplatin and PD98059. Conclusion PD98059 enhances the effects of oxaliplatin on colorectal cancer cells mediated by PUMA expression.