大蒜提取物二烯丙基化三硫对人膀胱癌T24细胞凋亡的影响  

EFFECTS OF GARLIC-DERIVED DATS ON APOPTOSIS OF HUMAN BLADDER CARCINOMA T24 CELLS

作　　者：王云彬[1] 谢立平[2] 秦杰[2] 郑祥毅[2] 白宇[2] 杨凯[2] 

机构地区：[1]内蒙古医学院附属医院泌尿外科,内蒙古呼和浩特010050 [2]浙江大学医学院附属第一医院泌尿外科

出　　处：《内蒙古医学院学报》2010年第2期77-81,共5页Acta Academiae Medicinae Neimongol

基　　金：浙江省中医药普通课题研究计划(2009CA057)

摘　　要：目的:研究大蒜提取物二烯丙基化三硫(diallyl trisulfide,DATS)在体外对T24细胞凋亡的诱导作用,并探讨其诱导凋亡的分子机制。方法:应用荧光染色形态学观察DATS作用后T24细胞凋亡形态学改变。并应用流式细胞仪检测细胞凋亡率的变化。采用蛋白质印迹法检测不同浓度DATS作用后T24细胞中caspase-3、PARP蛋白的表达,并进一步研究其分子机理。结果:DATS可明显诱导T24细胞细胞凋亡并呈显著剂量依赖性。DATS作用于T24细胞后,procaspase-3表达减少,同时出现PARP的裂解片段,并呈显著的剂量依赖性。DATS作用于T24细胞后,p-PDK1,p-Ser 473-Akt的表达逐渐降低,呈剂量依赖性,但t-Akt的表达不受影响。DATS作用于T24细胞后,Bax表达逐渐增高,Bcl-2的表达逐渐降低,呈显著的剂量依赖性。结论:DATS能诱导T24细胞凋亡,凋亡的诱导作用呈显著剂量依赖性。DATS诱导产生凋亡的机理可能通过抑制T24细胞PI3K/Akt信号通路的激活从而调节Bcl-2家族蛋白,并最终诱导凋亡发生。Objective：To investigate the effects of DATS on apoptosis of T24 cells and identify the altered signaling pathway underlying the response to DATS exposure.Methods：The induction of apoptosis by DATS was measured by acridine orange/ethidium bromide assays.The extent of apoptosis was quantified by flow cytometric analysis.Alterations in signaling events were determined in western bloting probing for akt proteins.The role of caspase-3,PARP,Bcl-2 family in apoptosis was analysed by western blotting.Results：Using the T24 human bladder cancer cell line,DATS treatment was resulted in induction of apoptosis in dose-dependent manner.Western bloting indicated that treatment of T24 cells with DATS was resulted in a dose-dependent activation of procaspase-3 and PARP proteins after DATS treatment.DATS treatment was resulted in an appreciable down-regulation of protein expression of phospho-PDK1 and phospho-Ser 473-Akt without an effect on total akt expression in T24 cells.DATS treatment of T24 cell lines was resulted in a decrease in antiapoptotic Bcl-2 and a concomitant increase in proapoptotic Bax proteins.Conclusion：DATS causes an inhibition of PI3K/Akt activation that results in modulations in Bcl-2 family proteins in such a way that the apoptosis of T24 cells is promoted.DATS could be developed as an agent for the management of bladder cancer.

关 键 词：膀胱癌 凋亡 二烯丙基化三硫 PI3K/AKT BCL-2 

分 类 号：R737.14[医药卫生—肿瘤]