Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

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 dosedependent 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.