多西他赛联合TRAIL诱导胃癌细胞SGC7901凋亡的作用  

Effect of combination of TRAIL and paclitaxel on human gastric cancer cell line SGC7901

作　　者：苏艳新[1] 王立[1] 

机构地区：[1]重庆医科大学附属第一医院消化内科,重庆400016

出　　处：《中国癌症杂志》2008年第4期262-266,共5页China Oncology

摘　　要：背景与目的:肿瘤坏死因子相关凋亡诱导配体能够诱导多种肿瘤细胞发生凋亡,但并不是所有的肿瘤细胞都对其敏感。以往研究表明一些化疗药物能够增强TRAIL所诱导的肿瘤细胞凋亡。本实验旨在探讨多西他赛联合TRAIL体外诱导胃癌细胞凋亡的作用及可能机制。方法:采用MTT法检测不同浓度(1、5、10、20、40μg/ml)及不同时间(12、24、36、48h)下多西他赛的抗癌活性并计算其亚毒性剂量。用流式细胞仪检测多西他赛(亚毒性剂量)及TRAIL(200ng/ml)单独及联合应用后SGC7901的凋亡率。RT-PCR法检测DR4、DR5、DcR1、DcR2、Caspase-8及Bcl-2 mRNA在加药前后的表达。结果:对照组(C组)、亚毒性剂量的多西他赛(P组)、TRAIL(T组)及两者联合(T+P)作用24h后胃癌细胞的凋亡率分别为2.09%、10.65%、7.79%和24.51%,T+P组凋亡率明显升高,与C组、T组、P组相比,差异均具有显著性(P<0.05)。多西他赛处理组DR5表达增加。结论:多西他赛与TRAIL具有协同抗胃癌作用,其机制可能与DR5 mRNA表达上调有关。Background and purpose： Tumor necrosis factor related apoptosis - inducing ligand （TRAIL） is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, but not all cancer cells . Past studies suggested that some chemotherapeutic drugs intensified the sensitivity of TRAIL induced apoptosis. We investigated the effect and potential mechanism of combined paclitaxel and TRAIL on apoptosis of human gastric cancer cell in vitro. Methods： SGC7901 cells were cultured with paelitaxel at different concentrations（ 1,5, 10, 20, 40 μg/ml） and different time（ 12, 24, 36, 48 hr）, methyl thiazolyl tetrazolium （MTT） assay was used to measure the anticancer activity of paclitaxel. The ability of TRAIL alone, paclitaxel alone and TRAIL in combination with paclitaxel to induce apoptosis was measured by a flow cytometer. Expression of DR4, DR5, DcR1, DcR2, Caspase-8 and Bcl-2 mRNA was examined by RT-PCR. Results： The apoptosis rates of control group（ C group）, paelitaxel group（ P group）, TRAIL group （ T group） and combination group（ T ＋ P） in 24 hr were 2.09%, 10.65%, 7.79% and 24.51%, respectively. The apoptosis rate in T ＋ P group was significantly higher than that in C group, T group and P group（ P 〈 0.05）. Before exposure to paclitaxel, DR5 mRNA expression was low and was up-regulated in SGC7901 cells after treatment with paclitaxel. Conclusions： There might be a synergistcal interaction between paclitaxel in terms of cytotoxieity and its mechanisms might be involved in the up-regulation of DR5 gene.

关 键 词：多西他赛 TRAIL 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]