DADS通过Rac1-ADF/cofilin1通路抑制人结肠癌SW480细胞迁移与侵袭  

Diallyl disulfide inhibits migration and invasion in human colon cancer SW480 cells through Rac1-ADF/cofilin1 pathway

作　　者：苏坚[1,2] 史玲[2,3] 周钰娟[2] 夏红[2] 廖前进[2] 董琳[2] 向姝霖[2] 苏琦[2] 

机构地区：[1]南华大学附属第二医院病理科,湖南省衡阳市421001 [2]湖南省高校肿瘤细胞与分子病理学重点实验室南华大学肿瘤研究所 [3]淄博市第三医院病理科

出　　处：《中国肿瘤临床》2013年第14期815-820,共6页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金青年科学基金项目(编号:31000629,81102854)资助~~

摘　　要：目的:研究二烯丙基二硫(diallyl disulfide,DADS)通过Rac1-ADF/cofilin1通路对人结肠癌SW480细胞迁移与侵袭的作用。方法:划痕愈合和侵袭实验分别检测DADS对SW480细胞迁移与侵袭的影响;RT-PCR与Western blot检测DADS对SW480细胞Rac1-ADF/cofilin1信号分子表达的作用。结果:40与50 mg/L DADS处理SW480细胞24 h后,穿膜细胞分别减少57.12%与64.59%(P<0.05)。处理48 h细胞迁移率分别为23.23%与12.87%,较对照组75.86%明显降低(P<0.05)。RT-PCR显示,45 mg/LDADS处理SW480细胞24、48 h后,与对照组比较Rac1、Rock1、PAK1、LIMK1和destrin mRNA分别显著下调(P<0.01);而cofilin1mRNA无显著性差异(P>0.05)。Western blot显示,45 mg/L DADS处理SW480细胞6、12、24、48 h后,与对照组比较Rac1、Rock1、PAK1、LIMK1和destrin蛋白分别呈时间依赖性下调(P<0.05),但cofilin1蛋白无显著性差异(P>0.05),而p-LIMK1和p-cofilin1表达分别呈时间依赖性下调(P<0.05)。结论:DADS可通过Rac1-ADF/cofilin1通路下调Rac1、Rock1、PAK1、LIMK1、p-LIMK1、destrin与p-cofilin1抑制SW480细胞迁移与侵袭。Objective： This work aims to investigate diallyl disulfide （DADS） inhibition of cell migration and invasion in human colon cancer SW480 cells through the Racl-ADF/cofilinl pathway. Methods： The potential of cell migration and invasion was examined by scratch healing assay and transwell membrane assay. The expression of Rac 1-ADF/cofilin 1 pathway was detected by RT-PCR and Western blot. Results： After the SW480 cells were treated with 40 and 50 mg·L^-1 of DADS for 24 h, the number of transmembrane cells through the Matrigel obviously decreased by 57.12% and 64.59%, respectively （P〈0.05）. After cell treatment for 48 h, the cell migration rates were 23.23% and 12.87%, which were significantly lower compared with the control group （75.86%; P〈0.05）. After the cells were treated with 45 mg.L-1 of DADS for 24 and 48 b, the expression ofRacl, Rockl, PAK1, LIMK1, and destrin mRNA respectively decreased compared with the control group （P〈0.05）. However, no significant difference was observed in the expression of cofilinl mRNA （P〉0.05）. After the treatment with 45 mg-L-1 of DADS for 6, 12, 24, and 48 h, the expression of Racl, Rock/, PAK1, LIMK1, and Destrin proteins respectively decreased in a time-dependent manner compared with the control group （P〈0.05）. However, no significant differences were observed in the expression of the cofilinl protein （P〉0.05）. Moreover, the expression of p-LIMK1 and p-cofilinl notably decreased in a time-dependent manner （P〈0.05）. Conclusion： DADS inhibits cell migration and invasion, which is related to the down-regulation ofRacl, Rockl, PAK1, LIMK1, p-LIMK1, p-cofilinl, and destrin through the Racl-ADF/cofilinl pathway.

关 键 词：二烯丙基二硫 结肠癌SW480细胞Rac1-ADF/cofilin1通路 迁移 侵袭 

分 类 号：R965[医药卫生—药理学] R735.35[医药卫生—药学]