Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, P.R. China.
Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
Oncol Rep. 2018 Jun;39(6):2797-2806. doi: 10.3892/or.2018.6345. Epub 2018 Mar 30.
Transforming growth factor‑β1 (TGF‑β1) has been demonstrated to promote epithelial‑mesenchymal transition (EMT), invasion and proliferation in tumors via the activation of Rac1 and β‑catenin signaling pathways. The present study investigated the effects of diallyl disulfide (DADS) on TGF‑β1‑induced EMT, invasion and growth of gastric cancer cells. TGF‑β1 treatment augmented EMT and invasion, concomitantly with increased expression of TGF‑β1, Rac1 and β‑catenin in gastric cancer cells. DADS downregulated the expression levels of TGF‑β1, Rac1 and β‑catenin. DADS, TGF‑β1 receptor inhibitor as well as Rac1 inhibitor antagonized the upregulation of the TGF‑β1‑induced expression of these genes, abolishing the enhanced effects of TGF‑β1 on EMT and invasion. Blocking the TGF‑β1 receptor through inhibition resulted in the decreased expression of Rac1 and β‑catenin. Rac1 inhibitor reduced the TGF‑β1‑induced β‑catenin expression. In addition, DADS and the aforementioned inhibitors attenuated the TGF‑β1‑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‑β1/Rac1 signaling by DADS may be responsible for the suppression of EMT, invasion and tumor growth in gastric cancer.
转化生长因子-β1（TGF-β1）已被证实可通过激活 Rac1 和β-连环蛋白信号通路促进肿瘤中的上皮间质转化（EMT）、侵袭和增殖。本研究探讨了二烯丙基二硫（DADS）对 TGF-β1 诱导的胃癌细胞 EMT、侵袭和生长的影响。TGF-β1 处理增强了 EMT 和侵袭，同时伴随着胃癌细胞中 TGF-β1、Rac1 和β-连环蛋白表达增加。DADS 下调了 TGF-β1、Rac1 和β-连环蛋白的表达水平。DADS、TGF-β1 受体抑制剂和 Rac1 抑制剂拮抗了 TGF-β1 诱导的这些基因表达的上调，消除了 TGF-β1 对 EMT 和侵袭的增强作用。通过抑制 TGF-β1 受体导致 Rac1 和β-连环蛋白表达降低。Rac1 抑制剂降低了 TGF-β1 诱导的β-连环蛋白表达。此外，DADS 和上述抑制剂减弱了 TGF-β1 在裸鼠中诱导的肿瘤生长以及 E-钙粘蛋白、波形蛋白、Ki-67 和 CD34 的表达变化。这些数据表明，DADS 通过阻断 TGF-β1/Rac1 信号通路可能是抑制胃癌 EMT、侵袭和肿瘤生长的原因。
