二烯丙基三硫通过Caspase-3途径诱导人胃癌MGC803细胞凋亡  

Diallyl Trisulfide Induces Apoptosis of Human Gastric Cancer Cell Line MGC803 Through Caspase-3 Pathway

作　　者：肖晓岚[1] 彭军[1] 苏琦[1] 向姝霖[1] 唐国华[1] 黄幼生[1] 周秀田[1] 

机构地区：[1]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《癌症》2006年第10期1247-1251,共5页Chinese Journal of Cancer

基　　金：湖南省科研计划重大专项(No.04SK1004);湖南省自然科学基金(No.03JJY5002);湖南省教育厅科研基金重点项目(No.04A047)~~

摘　　要：背景与目的:大蒜及其烯丙基硫化物具有抗肿瘤作用,但其具体的作用机制尚不十分清楚。本研究探讨二烯丙基三硫(diallyltrisulfide,DATS)诱导人胃癌MGC803细胞凋亡及凋亡过程中Caspase-3的变化及其意义。方法:采用荧光显微镜和电子显微镜观察以及流式细胞术和Westernblot检测等方法,观察DATS诱导MGC803细胞凋亡的作用及对活化的Caspase-3的影响。结果:在荧光显微镜及电子显微镜下,DATS作用的胃癌细胞出现了典型的凋亡形态学改变;流式细胞术检测出现明显的亚G1峰;12mg/L的DATS处理MGC803细胞0、4、8、12、24h后,活化的Caspase-3的表达率分别为1.9%、3.0%、7.3%、14.4%、27.6%,提示DATS呈时间依赖性促进活化的Caspase-3的表达;用特异的Caspase-3抑制剂预处理细胞后,再用12mg/LDATS处理细胞24h,与单用DATS组相比,凋亡率从23.0%降低到5.1%(P<0.01),提示Caspase-3的抑制剂能抑制DATS诱导的胃癌MGC803细胞凋亡。Westernblot显示酶原形式的Caspase-3被水解活化。结论:DATS诱导人胃癌MGC803细胞凋亡可能与活化Caspase-3有关。BACKGROUND ＆ OBJECTIVE. Garlic and the organosulfer compound from garlic have antitumor effects, but the mechanisms still remain unclear. This study was to investigate the changes and significance of caspase-3 activity in diallyl trisulfide （DATS）-induced apoptosis of human gastric cancer cell line MGC803. METHODS. Effects of DATS on the apoptosis of MGCS03 cells and the change of activated caspase-3 were observed under a fluorescent and an electron microscopy, and detected by flow cytometry and Western blot. RESULTS. After incubation with DATS, MGC803 cells showed typical apoptotic morphologic changes, and the apoptosis rate increased significantly. DATS activated caspase-3 in a time- dependent manner, the positive rates of activated caspase-3 were 1.9%, 3.0%, 7.3%, 14.4%, and 27.6% respectively in MGC-803 cells treated with 12 mg/L DATS for 0, 4, 8, 12 and 24 h. When treated with 12 mg/L DATS for 24 h, the apoptosis rate was significantly lower in the cells with pretreatment of Ac-DEVD-CHO （a caspase-3 inhibitor） than in the cells without pretreatment （5.1% vs. 23.0%, P〈0.01）, indicating that Ac-DEVD- CHO efficiently attenuated DATS-induced apoptosis of MGC803 cells. Moreover, pro-caspase3 was hydrolyzed and activated in DATS-treated MGC803 cells. CONCLUSION; DATS induces apoptosis in MGC803 cells which may be through the activation of caspase-3 pathway.

关 键 词：二烯丙基三硫/药理学 胃肿瘤 MGC803细胞 凋亡 CASPASE-3 

分 类 号：R735.2[医药卫生—肿瘤]