摘要
目的:探讨氟尿嘧啶(Fu)对重组人肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-relatedapoptosis-inducing ligand,TRAIL)诱导结肠癌细胞凋亡的影响及其作用机制。方法:采用四甲基偶氮唑蓝比色法检测Fu及联合rmhTRAIL对人结肠癌SW480的IC50值;流式细胞术检测不同浓度Fu与rmhTRAIL联合处理SW480 24 h后细胞的凋亡率;实时荧光定量PCR和Western印迹法检测不同浓度Fu与rmhTRAIL联合处理SW480 24 h后细胞survivin基因mRNA和蛋白表达变化。结果:细胞经药物处理24 h后,单用组IC50值为29.5μmol/L,Fu联合rmhTRAIL组IC50值为6.4μmol/L,高质量浓度联合组药物相互作用系数为0.92;Fu与rmhTRAIL联合作用24 h后,随Fu质量浓度增高survivin mRNA和蛋白的表达显著下调。结论:Fu能增强TRAIL诱导的结肠癌细胞凋亡,其机制可能与下调survivin表达有关。
Objective： To investigate the effect of fluorouvacil （Fu） on recombinant human tumor necrosis factor- related apoptosis-inducing ligand （TRAIL）-induced apoptosis in human colon cancer cells and the underlying mechanisms. Methods： The effect of Fu combined with rmhTRAIL on human colon cancer SW480 cell line was detected by M＇IT assay and ICS0 was calculated. The apoptotic rate after treatment for 24 h was detected by flow cytometry, survivin mRNA and protein level in SW480 cells was examined by real time-PCR and Western blot 24 h before or after treatments. Results： The IC50 for Fu treatment alone or Fu combined with rmhTRAIL was 29.5 8mol/L or 6.4 μmol/L, respectivelF The coefficient of drug in interaction in the high dosage group was 0.92. Compared with Fu or rmhTRAIL alone, the combination of Fu and rmhTRAIL could increase the apoptotic ratio significantly （P〈0.05）. Real time-PCR and Western blot showed that the expression of survivin in the combined group was obviously less than that in the group of Fu or rmhTRAIL alone. Conclusion： Fu promotes TRAIL- induced apoptosis in human colon cancer cells, which is likely involved in the down-regulation of survivin expression.
出处
《国际病理科学与临床杂志》
CAS
2012年第6期469-472,共4页
Journal of International Pathology and Clinical Medicine
基金
衡阳市科技局课题(2010KS35)~~
