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Open Access Research article

Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

Chen-Chieh Yang12, Shun-Fu Chang3, Jian-Kang Chao45, Yi-Liang Lai6, Wei-En Chang1, Wen-Hsiu Hsu6 and Wu-Hsien Kuo167*

Author Affiliations

1 Division of Gastroenterology, Department of Internal Medicine, Armed-Forces Hualien General Hospital, Hualien 97144, Taiwan

2 Mennonite Christian Hospital, Hualien 97059, Taiwan

3 Biophotonics & Molecular Imaging Research Center, National Yang Ming University, Taipei 11221, Taiwan

4 Department of Psychiatry, Yuli branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan

5 Department of Health Administration, Tuz Chi College of Technology, Hualien, Taiwan

6 Division of Gastroenterology, Department of Internal Medicine, Armed-Forces Taichung General Hospital, Taiping District, Taichung City 41168, Taiwan

7 School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan

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BMC Cancer 2014, 14:112  doi:10.1186/1471-2407-14-112

Published: 20 February 2014

Abstract

Background

Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects.

Methods

Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects.

Results

Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs.

Conclusions

These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis.

Keywords:
AMP-activated protein kinase; Hepatocellular carcinoma; Intercellular adhesion molecule-1; Resistin; Vascular cell adhesion molecule-1