目的

探讨紫杉醇对肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis inducing ligand，TRAIL）诱导MCF-7乳腺癌细胞系凋亡的影响及其作用机制。

方法

MTT法检测不同浓度的单药紫杉醇组、单药TRAIL组和联合给药组1（同时给予紫杉醇和TRAIL）、联合给药组2（先给予TRAIL再给予紫杉醇）、联合给药组3（先给予紫杉醇再给予TRAIL）对MCF-7细胞的抑制作用；流式细胞术Annexin V-FITC／PI染色法检测不同给药方案对细胞凋亡的影响；RT-PCR法检测紫杉醇对MCF-7细胞TRAIL受体——死亡受体（death receptor，DR）4与5表达水平的影响。

结果

紫杉醇对MCF-7细胞的抑制作用随药物浓度提高而增强，呈剂量依赖性；MCF-7细胞对TRAIL呈一定程度的耐药；联合给药组1（同时给予紫杉醇和TRAIL）与紫杉醇单药组1、TRAIL单药组1比较无协同作用（CDI＝1.00，＞0.85）；联合给药组2（先给予TRAIL再给予紫杉醇）与紫杉醇单药组1、TRAIL单药组2比较亦无协同作用（CDI＝0.87，＞0.85）；联合给药组3（先给予紫杉醇再给予TRAIL）与紫杉醇单药组2、TRAIL单药组1比较可见协同作用（CDI＝0.46，＜0.75）。先给予紫杉醇再给予TRAIL联合给药组（联合给药组3）较单药组凋亡细胞数目多。紫杉醇可诱导MCF-7细胞DR5表达上调，而对DR4表达水平无影响。

结论

紫杉醇与TRAIL联合可协同抑制MCF-7细胞生长，机制可能与紫杉醇诱导的死亡受体5 mRNA表达上调有关。

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.