Diallyl disulfide inhibits colon cancer metastasis by suppressing Rac1-mediated epithelial-mesenchymal transition

被引：40
作者：
Xia, Longzheng [1 ,2 ]
Lin, Jingguan [1 ,2 ]
Su, Jian [3 ]
Oyang, Linda [1 ,2 ]
Wang, Heran [1 ,2 ]
Tan, Shiming [1 ,2 ]
Tang, Yanyan [1 ,2 ]
Chen, Xiaoyan [1 ,2 ]
Liu, Wenbin [1 ,2 ]
Luo, Xia [1 ,2 ]
Tian, Yutong [1 ,2 ]
Liang, Jiaxin [1 ,2 ]
Su, Qi [3 ]
Liao, Qianjin [1 ,2 ]
Zhou, Yujuan [1 ,2 ]
机构：
[1] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Key Lab Translat Radiat Oncol, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China
[2] Hunan Canc Hosp, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China
[3] Univ South China, Canc Res Inst, Hengyang, Hunan, Peoples R China
来源：
ONCOTARGETS AND THERAPY | 2019年 / 12卷
基金：
中国国家自然科学基金;
关键词：
colon cancer; diallyl disulfide; Ras related C3 botulinum toxin substrate1; epithelial-mesenchymal transition; metastasis; RAC1; ACTIVATION; DOWN-REGULATION; CELL-MIGRATION; BETA-CATENIN; RHO GTPASES; PROLIFERATION; EMT; PHOSPHORYLATION; MOTILITY; PATHWAY;
D O I：
10.2147/OTT.S208738
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Background: Prevention of epithelial-mesenchymal transition (EMT) provides a novel treatment strategy for tumor metastasis. Our previous studies have shown that diallyl disulfide (DADS) inhibits Ras related C3 botulinum toxin substrate1 (Rac1) expression, being a potential agent that suppresses migration and invasion of colon cancer cells. The study provides information on the underlying mechanisms. Methods: The expression of Rac1 and EMT markers (vimentin, N-cadherin and E-cadherin) in colon cancer samples was detected. Colon cancer cell lines treated with or without DADS were used to examine EMT markers, Rac1 and its related molecules. Various cell functions related to metastasis were performed in vitro, and further confirmed in vivo. Results: Rac1 was highly expressed in colon cancer, and associated with aberrant expression of EMT markers and poor prognosis. Rac1 overexpression induced cell migration and invasion in vitro and metastasis in vivo with down-regulation of E-cadherin and up-regulation of N-cadherin, vimentin, and snail1, whereas inhibition of Rac1 impaired the oncogenic function. DADS suppressed Rac1 expression and activity via inhibition of PI3K/Akt pathway, thus suppressing EMT and invasion and migration of colon cancer cells. The tumor inhibition of DADS was enhanced by knockdown of Rac1, but antagonized by overexpression of Rac1. We further found that DADS blocked EMT via targeting the Rac1-mediated PAK1-LIMK1-Cofilins signaling. Conclusion: Rac1 is a potential target molecule for the inhibitory effect of DADS on EMT and invasion and metastasis of colon cancer cells.
引用
收藏
页码：5713 / 5728
页数：16
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