Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell

Wenbo Meng; Xun Li; Zhongtian Bai; Yan Li; Jinqiu Yuan; Tao Liu; Jun Yan; Wence Zhou; Kexiang Zhu; Hui Zhang; Yumin Li

doi:10.1371/journal.pone.0090660

Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell

PLoS One. 2014 Feb 28;9(2):e90660. doi: 10.1371/journal.pone.0090660. eCollection 2014.

Authors

Wenbo Meng¹, Xun Li², Zhongtian Bai², Yan Li³, Jinqiu Yuan⁴, Tao Liu⁵, Jun Yan², Wence Zhou², Kexiang Zhu², Hui Zhang², Yumin Li⁵

Affiliations

¹ The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou, Gansu Province, China ; Special Minimally Invasive Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China.
² The Second Department of General Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China.
³ Department of Immunology, Cleveland Clinic, Cleveland, Ohio, United States of America.
⁴ Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
⁵ The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou, Gansu Province, China.

Abstract

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Apoptosis / genetics
Blotting, Western
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement / genetics
Cells, Cultured
Gene Expression Regulation, Neoplastic
Human Umbilical Vein Endothelial Cells / metabolism
Human Umbilical Vein Endothelial Cells / physiology
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism*
Neovascularization, Physiologic / genetics
Neovascularization, Physiologic / physiology
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism*
Vascular Endothelial Growth Factor Receptor-2 / metabolism
alpha-Fetoproteins / genetics
alpha-Fetoproteins / metabolism*

Substances

Vascular Endothelial Growth Factor A
alpha-Fetoproteins
KDR protein, human
Vascular Endothelial Growth Factor Receptor-2
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9

Grants and funding

This work was supported by the Natural Science Foundation of China (31270532, 31270543), “Fundamental Research Funds for the Central Universities” (lzujbky- 2010-144; lzujbky-2012-167), West Light Foundation of The Chinese Academy of Science (2009-236), and Health Industry Research Project of Gansu Province (GSWST 2011- 04). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.