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Resveratrol Inhibits Invasion and Metastasis of Colorectal Cancer Cells via MALAT1 Mediated Wnt/β-Catenin Signal Pathway

机译:白藜芦醇通过MALAT1介导的Wnt /β-Catenin信号通路抑制结直肠癌细胞的侵袭和转移

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摘要

Resveratrol, extracted from Chinese herbal medicine Polygonum cuspidatum, is known to inhibit invasion and metastasis of human colorectal cancer (CRC), in which long non-coding Metastasis Associated Lung Adenocarcinoma Transcript 1 (RNA-MALAT1) also plays an important role. Using MALAT1 lentiviral shRNA and over-expression constructs in CRC derived cell lines, LoVo and HCT116, we demonstrated that the anti-tumor effects of resveratrol on CRC are through inhibiting Wnt/β-catenin signaling, thus the expression of its target genes such as c-Myc, MMP-7, as well as the expression of MALAT1. In detail, resveratrol down-regulates MALAT1, resulting in decreased nuclear localization of β-catenin thus attenuated Wnt/β-catenin signaling, which leads to the inhibition of CRC invasion and metastasis. This finding of ours surely provides important pre-clinical evidence supporting future use of resveratrol in prevention and treatment of CRC.
机译:从中草药虎杖中提取的白藜芦醇可抑制人结肠直肠癌(CRC)的侵袭和转移,其中长期非编码转移相关的肺腺癌转录本1(RNA-MALAT1)也起着重要作用。使用MALAT1慢病毒shRNA和在CRC衍生的细胞系LoVo和HCT116中的过表达构建体,我们证明了白藜芦醇对CRC的抗肿瘤作用是通过抑制Wnt /β-catenin信号传导,从而使其靶基因如c-Myc,MMP-7以及MALAT1的表达。详细地说,白藜芦醇下调MALAT1,导致β-catenin的核定位降低,从而减弱Wnt /β-catenin信号传导,从而导致CRC侵袭和转移受到抑制。我们的这一发现无疑提供了重要的临床前证据,支持白藜芦醇在CRC预防和治疗中的未来应用。

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