摘要
目的探讨二甲双胍能否增强膀胱癌5637细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导细胞凋亡的敏感性及其机制。方法 MTT法检测不同浓度TRAIL(0、10、20、40、60、100 ng/mL)和二甲双胍(10 mM)联合用药对膀胱癌5637细胞的增殖抑制作用。Annexin V-FITC/PI双染检测二甲双胍对TRAIL诱导5637细胞凋亡的影响。Western blot检测二甲双胍和/或TRAIL干预5637细胞24小时后对caspase-8、caspase-3、PARP、DR4、DR5和c-FLIPL表达的影响。结果二甲双胍可增强TRAIL对膀胱癌5637细胞的增殖抑制作用和凋亡诱导作用,二甲双胍单独用药并未上调DR4和DR5表达,但显著下调c-FLIPL表达。结论二甲双胍显著增强膀胱癌5637细胞对TRAIL的敏感性,其机制可能与二甲双胍下调c-FLIPL表达有关。
Objective To investigate the effect of metformin in sensitizing bladder cancer cells 5637 to TRAIL-induced apoptosis and the possible mechanism. Methods The cell viability was measured using MTT assay,while cell apoptosis was detected using flow cytometry with Annexin V-FITC/PI staining. Proteins of the TRAIL signaling pathway were measured by Western blot. Results Metformin markedly potentiated the TRAIL-induced apoptosis inbladder cancercells 5637. To elucidate the underlying mechanism,metformin alone did not alter the expression levels of death receptor 4 (DR4 )and DR5 ,but significantly reduced the cellular Fas-asso-ciated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE)inhibitory protein c-FLIPL levels,contributing toward the sensitization to TRAIL. Conclusions Metformin sensitizes bladder cancer cells 5637to TRAIL-induced apoptosis through the downregulation of c-FLIPL.
出处
《泌尿外科杂志（电子版）》
2014年第1期21-25,36,共6页
Journal of Urology for Clinicians(Electronic Version)
