Abstract:

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.

Key words: Breast neoplasms, aclitaxel, Tumor necrosis factor, Chemotherapy