Abstract 1689: Resveratrol inhibits epithelial-to-mesenchymal transition and metastasis in colorectal cancer through regulating Snail/E-cadherin expression by TGFβ1/Smads signaling pathway

Abstract

Abstract Resveratrol has been an ideal alternative drug in the therapy of different cancers including colorectal cancer (CRC). Since the underlying mechanisms of resveratrol on the invasion and metastasis of CRC have not been fully elucidated, and epithelial-to-mesenchymal transition (EMT) is a key process associated with the progression of CRC, here we aimed to investigate the potential mechanism of resveratrol. We investigated the anticancer effect of resveratrol against LoVo cells in vitro and in vivo. In vivo, the impact of resveratrol on invasion and metastasis was investigated by mice tail vein injection model and mice orthotopic transplantation tumor model. In vivo imaging was applied to observe the lungs metastases, and hemaoxylin-eosin (HE) staining was used to evaluate metastatic lesions from lung metastases or hepatic metastases. In vitro, impact of resveratrol on the migration and invasion of LoVo cells was evaluated by transwell assay. Inhibition effect of resveratrol on TGF-β-induced EMT was examined by morphological observation. Epithelial phenotype marker E-cadherin and mesenchymal phenotype marker Vimentin were detected by western blot and immunofluorescence. The promoter activity of E-cadherin was measured using a dual-luciferase assay kit. The mRNA expression of Snail and E-cadherin was measured by RT-PCR. We demonstrated that, resveratrol inhibited the lung metastases of CRC LoVo cells in vivo. In addition, resveratrol reduced the rate of lung metastases and hepatic metastases in mice orthotopic transplantation. In vitro, TGF-β1-induced EMT promoted the invasion and metastasis of CRC, reduced the expression of E-cadherin and elevated the expression of Vimentin, and activated the TGF-β1/Smads signaling pathway. But resveratrol could inhibit the invasive and migratory ability of LoVo cells in a concentration-dependent manner, increased the expression of E-cadherin, repressed the expression of Vimentin, as well as the inhibition of TGF-β1/Smads signaling pathway. Meanwhile, resveratrol reduced the level of EMT-inducing transcription factors Snail and the transcription of E-cadherin during the initiation of TGF-β1-induced EMT. Our new findings provided evidence that, resveratrol could inhibit EMT in CRC through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression, and this might the potential mechanism of resveratrol on the inhibition of invasion and metastases in CRC. Citation Format: Qing Ji, Zhifen Han, Lihong Zhou, Hua Sui, Xuan Liu, Jianlin Ren, Fenggang Hou, Ronghua Zhao, Qi Li. Resveratrol inhibits epithelial-to-mesenchymal transition and metastasis in colorectal cancer through regulating Snail/E-cadherin expression by TGFβ1/Smads signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1689.