Mechanism of apoptosis induced by Paclitaxel combined with TRAIL in the MCF-7 breast cancer cell line

Objective To determine the interaction between Paclitaxel and TRAIL(tumor necrosis factor-related apoptosis inducing ligand) in MCF-7 breast cancer cell line and investigate the possible mechanism.Methods The inhibitory rates of different concentrations of Paclitaxel,TRAIL alone or different combinations of Paclitaxel and TRAIL on MCF-7 cells were examined by MTT assay.MCF-7 cells of the control group,the TRAIL group,the Paclitaxel group and the combination group were stained by Annexin V-FITC/PI;and the apoptosis rates were detected by flow cytometry.At mRNA levels,DR4 and DR5 of MCF-7 cells treated by Paclitaxel were semi-qualified by RT-PCR.Results MTT assay showed that MCF-7 cells were sensitive to Paclitaxel in a dose-dependent manner and less sensitive to TRAIL.MTT assay also showed different combination schemes had different inhibitory effects.There were not synergistic effects in Sheme 1(MCF-7 cells were treated by Paxlitaxel and TRAIL simultaneously,CDI=1.00,0.85) and Sheme 2(MCF-7 cells were treated with TRAIL firstly and successively treated with Paclitaxel,CDI=0.87,0.85),but synergistic effects could be seen in Sheme 3(MCF-7 cells treated with Paclitaxel firstly and successively treated with TRAIL,CDI=0.46,0.75)).The synergism of Sheme 3 was verified by Annexin V-FITC/PI assay.DR4 and DR5 were detected by RT-PCR at mRNA levels,DR5 was up-regulated by Paclitaxel,but DR4 was not changed significantly.Conclusions A synergism could be seen when MCF-7 cells were treated with Paclitaxel followed by TRAIL,the mechanism of which may be related to the up-regulation of DR5 induced by Paclitaxel at the mRNA level.