Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 21, 2008; 14(15): 2308-2313
Published online Apr 21, 2008. doi: 10.3748/wjg.14.2308
Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro
Ji-Kun Li, Liang Yu, Yun Shen, Li-Sheng Zhou, Yi-Cheng Wang, Jian-Hai Zhang
Ji-Kun Li, Liang Yu, Yun Shen, Li-Sheng Zhou, Jian-Hai Zhang, Department of General Surgery, Affiliated First People’s Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Yi-Cheng Wang, Department of Pathology, Affiliated First People’s Hospital, Shanghai Jiaotong University, Shanghai 200080, China
Author contributions: Li JK and Yu L contributed equally to this work; Li JK and Yu L designed the research; Yu L, Shen Y, Zhang JH and Wang YC performed the research; Li JK, Zhou LS and Wang YC contributed new reagents/analytic tools; Yu L, Shen Y and Wang YC analyzed the data; and Li JK and Yu L wrote the paper.
Correspondence to: Liang Yu, Department of General Surgery, Affiliated First People’s Hospital, Shanghai Jiaotong University, Shanghai 200080, China. cherish_yu3k@hotmail.com
Telephone: +86-21-63240090-3112
Fax: +86-21-66302029
Received: January 3, 2008
Revised: February 25, 2008
Published online: April 21, 2008
Abstract

AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro.

METHODS: Human colorectal cancer cell line SW480 was treated with AMD3100 at different final concentrations. 3-(4,5-dimethylthiazol-2-yl)-2.5-dipheny-tetrazolium bromide (MTT) assay was used to detect the effect of AMD3100 on cell proliferation. The invasion ability of SW480 cells was determined by cell invasion assay kit. In the presence of AMD3100, the CXCL12-mediated migratory response of SW480 cells was tested by classical chemotaxis assays. RT-PCR analysis and Western blotting were used to detect the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in SW480 cells.

RESULTS: Cell viability was significantly suppressed by AMD3100 in a dose-dependent manner. AMD3100 (100 and 1000 ng/mL) significantly inhibited the invasion ability of SW480 cells. Treatment with AMD3100 markedly reduced the expression of VEGF and MMP-9 but not MMP-2 in SW480 cells.

CONCLUSION: The CXCL12/CXCR4 system is an important mediator of proliferation and invasion of CXCR4-expressing colorectal cancer cells. AMD3100 inhibited invasion and metastasis activity of the colorectal cancer cell line SW480 through down-regulation of VEGF and MMP-9 expression.

Keywords: Colorectal cancer; CXCR4; Vascular endothelial growth factor; MMPs; Invasion