Diallyl disulfide inhibits TGF-β1-induced upregulation of Rac1 and β-catenin in epithelial-mesenchymal transition and tumor growth of gastric cancer

作者：Su, Bo; Su, Jian; Zeng, Ying; Ding, En; Liu, Fang; Tan, Tuo; Xia, Hong; Wu, You-Hua; Zeng, Xi; Ling, Hui; Jiang, Hao; Ai, Xiao-Hong^*; Su, Qi^*

来源：Oncology Reports, 2018, 39(6): 2797-2806.

DOI：10.3892/or.2018.6345

• diallyl disulfide
• TGF-beta 1
• Rac1
• beta-catenin
• gastric cancer cell epithelial-mesenchymal transition
• invasion

Transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated to promote epithelial-mesenchymal transition (EMT), invasion and proliferation in tumors via the activation of Rac1 and beta-catenin signaling pathways. The present study investigated the effects of diallyl disulfide (DADS) on TGF-beta 1-induced EMT, invasion and growth of gastric cancer cells. TGF-beta 1 treatment augmented EMT and invasion, concomitantly with increased expression of TGF-beta 1, Rac1 and beta-catenin in gastric cancer cells. DADS downregulated the expression levels of TGF-beta 1, Rac1 and beta-catenin. DADS, TGF-beta 1 receptor inhibitor as well as Rac1 inhibitor antagonized the upregulation of the TGF-beta 1-induced expression of these genes, abolishing the enhanced effects of TGF-beta 1 on EMT and invasion. Blocking the TGF-beta 1 receptor through inhibition resulted in the decreased expression of Rac1 and beta-catenin. Rac1 inhibitor reduced the TGF-beta 1-induced beta-catenin expression. In addition, DADS and the aforementioned inhibitors attenuated the TGF-beta 1-induced tumor growth and the expression changes of E-cadherin, vimentin, Ki-67 and CD34 in nude mice. These data indicated that the blockage of TGF-beta 1/Rac1 signaling by DADS may be responsible for the suppression of EMT, invasion and tumor growth in gastric cancer.

• 出版日期2018-6
• 单位南华大学; 湖南中医药大学; 湖南大学