已发表论文

二烯丙基二硫化物通过抑制 Rac1 介导的上皮 - 间质转化遏制结肠癌转移

 

Authors Xia L, Lin J, Su J, Oyang L, Wang H, Tan S, Tang Y, Chen X, Liu W, Luo X, Tian Y, Liang J, Su Q, Liao Q, Zhou Y

Received 14 March 2019

Accepted for publication 6 June 2019

Published 16 July 2019 Volume 2019:12 Pages 5713—5728

DOI https://doi.org/10.2147/OTT.S208738

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Rachel Predeepa

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava

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.
Keywords: colon cancer, diallyl disulfide, Ras related C3 botulinum toxin substrate1, epithelial-mesenchymal transition, metastasis




Figure 4 DADS regulates colon cancer cell invasive and migratory capabilities by...