Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Sep 28, 2009; 15(36): 4547-4555
Published online Sep 28, 2009. doi: 10.3748/wjg.15.4547
Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action
Hong Sun, Juan Ren, Qing Zhu, Fan-Zhong Kong, Lei Wu, Bo-Rong Pan
Hong Sun, Juan Ren, Qing Zhu, Fan-Zhong Kong, Lei Wu, Cancer Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Bo-Rong Pan, Cancer Institute and Clinic, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Author contributions: Sun H, Ren J and Zhu Q contributed equally to this work; Ren J designed research; Ren J, Kong FZ and Wu L performed research; Sun H and Zhu Q contributed new reagents/analytical tools; Sun H, Ren J and Zhu Q analyzed data; Sun H, Ren J and Pan BR wrote the paper.
Correspondence to: Hong Sun, Associate Professor, Cancer Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China. araa@sohu.com
Telephone: +86-29-85324029 Fax: +86-29-84333065
Received: June 26, 2009
Revised: August 1, 2009
Accepted: August 8, 2009
Published online: September 28, 2009
Abstract

AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action.

METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.

RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dose-dependent manner (P < 0.05). Rho kinase inhibitor, Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05), but the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis.

CONCLUSION: LPA stimulated proliferation, adhesion, migration of SW480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K-AKT/PKB signal pathways may be involved.

Keywords: Lysophosphatidic acid; Colon cancer; Proliferation; Apoptosis; Adhesion; Migration; Signal pathway