Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway

Qing Ji; Xuan Liu; Xiaoling Fu; Long Zhang; Hua Sui; Lihong Zhou; Jian Sun; Jianfeng Cai; Jianmin Qin; Jianlin Ren; Qi Li

doi:10.1371/journal.pone.0078700

Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway

PLoS One. 2013 Nov 11;8(11):e78700. doi: 10.1371/journal.pone.0078700. eCollection 2013.

Authors

Qing Ji¹, Xuan Liu, Xiaoling Fu, Long Zhang, Hua Sui, Lihong Zhou, Jian Sun, Jianfeng Cai, Jianmin Qin, Jianlin Ren, Qi Li

Affiliation

¹ Department of Medical Oncology, Shuguang Hospital; Shanghai University of Traditional Chinese Medicine, Shanghai, China ; Interventional Cancer Institute & Department of General Surgery, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

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.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Cell Nucleus / genetics
Cell Nucleus / metabolism
Cell Nucleus / pathology
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / pathology*
Female
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Male
Matrix Metalloproteinase 7 / biosynthesis
Matrix Metalloproteinase 7 / genetics
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis
Proto-Oncogene Proteins c-myc / biosynthesis
Proto-Oncogene Proteins c-myc / genetics
RNA, Long Noncoding / biosynthesis*
RNA, Long Noncoding / genetics
RNA, Neoplasm / biosynthesis*
RNA, Neoplasm / genetics
Resveratrol
Stilbenes / pharmacology*
Wnt Signaling Pathway / drug effects*
Wnt Signaling Pathway / genetics
beta Catenin / genetics
beta Catenin / metabolism

Substances

Antineoplastic Agents, Phytogenic
MALAT1 long non-coding RNA, human
MYC protein, human
Proto-Oncogene Proteins c-myc
RNA, Long Noncoding
RNA, Neoplasm
Stilbenes
beta Catenin
MMP7 protein, human
Matrix Metalloproteinase 7
Resveratrol

Grants and funding

This work was supported by National Natural Science Foundation of China (81202812, 81303102, 81303103), Program of Shanghai Municipal Education Commission (2011JW57, 12YZ058), Shanghai Municipal Health Bureau (ZYSNXD-CC-YJXYY-JS20, 2011ZJ030, 20114Y001, 20114037), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (C10dz2220200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.