紫杉醇联合肿瘤坏死因子相关凋亡诱导配体诱导MCF-7乳腺癌细胞系凋亡机制的研究

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 inducingligand，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AnnexinV—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（deathreceptor，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5mRNA表达上调有关。

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 ap...