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

  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、48h后，与对照组比较Rac1、Rock1、PAK1、LIMK1和destrin mRNA分别显著下调（P < 0.01）；而cofilin1 mRNA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。 

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

  Objective  This work aims to investigate diallyl disulfide (DADS) inhibition of cell migration and invasion in human colon cancer SW480 cells through the Rac1-ADF/cofilin1 pathway.   Methods  The potential of cell migration and invasion was examined by scratch healing assay and transwell membrane assay. The expression of Rac1-ADF/cofilin1 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 h, the expression of Rac1, Rock1, 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 cofilin1 mRNA (P>0.05). After the treatment with 45 mg·L-1 of DADS for 6, 12, 24, and 48 h, the expression of Rac1, Rock1, 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 cofilin1 protein (P>0.05). Moreover, the expression of p-LIMK1 and p-cofilin1 notably decreased in a time-dependent manner (P < 0.05).   Conclusion   DADS inhibits cell migration and invasion, which is related to the down-regulation of Rac1, Rock1, PAK1, LIMK1, p-LIMK1, p-cofilin1, and destrin through the Rac1-ADF/cofilin1 pathway.