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


CONCLUSIONS
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.
Cancer Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China. araa@sohu.com.
Hong
H
Sun
Juan
J
Ren
Qing
Q
Zhu
Fan-Zhong
FZ
Kong
Lei
L
Wu
Bo-Rong
BR
Pan
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*
D008246:Lysophospholipids; C032881:lysophosphatidic acid