TRAIL与低剂量5-Fu联用高效诱导大肠癌细胞凋亡的研究  

The Apoptosis-inducing Effect of TRAIL and Low-concentration 5-Fu on Colon Cancer Cells

作　　者：徐莉红[1] 邓长生[1] 刘诗权[1] 

机构地区：[1]武汉大学中南医院消化内科,430071

出　　处：《实用癌症杂志》2003年第2期152-154,共3页The Practical Journal of Cancer

摘　　要：目的　探讨肿瘤坏死因子相关凋亡诱导配体 (TRAIL)与 5 -Fu联用是否存在协同性杀伤大肠癌细胞的作用 ,以及这种杀伤作用的可能机制。方法　常规培养大肠腺癌细胞株HT 2 9。TRAIL、5 -Fu、或 2药联用 2 4h ,采用MTT法测试细胞毒作用 ,应用流式细胞术检测细胞凋亡比例 ,透射电镜下观察亚细胞形态。结果　①HT 2 9细胞对TRAIL不敏感 ,10 0ng/mlTRAIL只能杀伤 4.5 0 %± 0 .2 6%的细胞 ,ID 5 0 >10 0 0ng/ml。细胞对 5 -Fu相对敏感 ,存在剂量依赖性细胞毒效应 ,这种效应主要通过诱导细胞凋亡实现。②TRAIL与阿霉素联用呈现高效协同作用 ,表现为亚毒性浓度TRAIL (10 0ng/ml)与亚毒性浓度5 -Fu(10 0 μg/ml)联用可杀死 60 .0 0 %± 0 .45 %的HT 2 9细胞。③流式细胞术分析及透射电镜观察证实协同性杀伤作用主要通过诱导细胞凋亡实现。结论　大肠腺癌细胞株HT2 9对TRAIL不敏感 ,但TRAIL与亚毒性浓度 5 -Fu联用表现出高效的杀灭肿瘤细胞作用 。Objective This study aims to detect whether TRAIL can synergize with 5 Fu to kill colon cancer cell line HT29,and its possible mechanism.Methods HT29 cells were cultured in the regular condition.MTT(microculture tetrazolium dye) was used to evaluate the cytotoxic effects at 24 hours after TRAIL and 5 Fu,alone or combined,were added to cells.Flow Cytometry Assay was also used to test the apoptosis proportion among these cells.Electron microscopy was used to observe the subcellular morphologic change.Results ①HT29 cells were not sensitive to TRAIL.The rate of killing was 4.50%±0.26% with TRAIL concenlzation of 100 ng/ml.And ID 50>1 000 μg/ml;The cells were comparatively more responsive to 5 Fu with an apparent dose effect relationship.This cytotoxicity was mainly due to cell apoptosis.②The combination of TRAIL and 5 Fu presented synergistic effect on HT29 cells.Subtoxic concentration of TRAIL(100 ng/ml) together with subtoxic concentration of 5 Fu(100 μg/ml),could kill 60.00% ±0.45% of HT29 cells.③The cytotoxicity was mainly attributed to cell apoptosis as proved by flow cytometry assay and electron microscopy.Conclusion TRAIL can synergize with subtoxic 5 Fu to effectively kill colon cancer cell line HT29 even these cells are resistant to TRAIL alone.Apoptosis is the main mechanism of this killing effect.

关 键 词：大肠癌 细胞凋亡 肿瘤坏死因子相关凋亡诱导配体 5-Fu 协同杀伤作用 作用机制 

分 类 号：R735.34[医药卫生—肿瘤] R730.53[医药卫生—临床医学]