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

  • 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、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。

     

    Abstract:
      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.

     

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