Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression.
Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression.
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白藜芦醇通过 TGF-β1/Smads 信号通路介导的 Snail/E-cadherin 表达抑制结直肠癌的上皮间质转化。
DOI：
10.1186/s12885-015-1119-y
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发表时间：
2015-03-05
期刊：
影响因子：
3.8
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Ji Q;Liu X;Han Z;Zhou L;Sui H;Yan L;Jiang H;Ren J;Cai J;Li Q
从葡萄中提取的白藜芦醇已成为治疗包括结直肠癌在内的多种癌症的理想替代药物。鉴于白藜芦醇对结直肠癌侵袭转移的作用机制尚未完全阐明，而上皮间充质转化是结直肠癌发生发展的关键环节，本研究旨在探讨白藜芦醇抑制转化生长因子-β-1诱导的结直肠癌细胞间充质转化的可能机制。我们研究了白藜芦醇在体内外对LoVo细胞的抗癌作用。采用小鼠尾静脉注射模型和小鼠原位移植瘤模型，观察白藜芦醇对肿瘤侵袭转移的影响。活体显像观察肺转移灶，苏木精-伊红(HE)染色评价转移灶。体外用Transwell法检测白藜芦醇对LoVo细胞迁移和侵袭的影响。通过形态学观察白藜芦醇对转化生长因子-β诱导的子宫内膜间质转化的抑制作用。免疫印迹和免疫荧光法检测上皮细胞表型标志物E-钙粘附素和间质表型标志物Vimentin。用双荧光素酶分析试剂盒检测E-钙粘素启动子活性。逆转录-聚合酶链式反应(RT-PCR)检测Snail和E-cadherin的mRNA表达。我们证明，白藜芦醇在体内抑制了LoVo细胞的肺转移。此外，白藜芦醇还降低了小鼠原位移植的肺转移率和肝转移率。在体外，转化生长因子-β-1诱导的EMT促进结直肠癌的侵袭和转移，降低E-钙粘素的表达，上调波形蛋白的表达，并激活转化生长因子-β-1/Smads信号通路。但白藜芦醇可浓度依赖地抑制LoVo细胞的侵袭和迁移能力，上调E-钙粘附素的表达，抑制Vimentin的表达，并抑制转化生长因子-β-1/Smads信号通路。同时，在转化生长因子-β-1诱导的子宫内膜间质转化过程中，白藜芦醇可降低子宫内膜间质转化诱导转录因子Snail的水平和E-钙粘素的转录水平。我们的新发现为白藜芦醇通过转化生长因子-β-1/Smads信号通路介导Snail/E-钙粘素表达抑制结直肠癌内皮细胞转移提供了证据，这可能是白藜芦醇抑制结直肠癌侵袭转移的可能机制。
Resveratrol extracted from grape 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 on the inhibition of TGF-β1-induced EMT in CRC LoVo cells. 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. 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. Promoter activity of E-cadherin was measured using a dual-luciferase assay kit. mRNA expression of Snail and E-cadherin was measured by RT-PCR. We demonstrated that, resveratrol inhibited the lung metastases of 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 E-cadherin expression and elevated the Vimentin expression, 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, increase the expression of E-cadherin, repress 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.
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影响因子：
3.7
作者：
Ji Q;Liu X;Fu X;Zhang L;Sui H;Zhou L;Sun J;Cai J;Qin J;Ren J;Li Q
通讯作者：
Li Q
DOI：
10.1016/j.biocel.2007.07.011
发表时间：
2007-01-01
影响因子：
4
作者：
Guarino, Marcello
通讯作者：
Guarino, Marcello
影响因子：
9
作者：
通讯作者：
--
影响因子：
--
作者：
Vergara, Daniele;Simeone, Pasquale;Maffia, Michele
通讯作者：
Maffia, Michele
影响因子：
9.7
作者：
Vergara, Daniele;Valente, Concetta Maria;Maffia, Michele
通讯作者：
Maffia, Michele