Lysophosphatidic acid prevents apoptosis of Caco-2 colon cancer cells via activation of mitogen-activated protein kinase and phosphorylation of Bad.

摘要: Lysophosphatidic acids (LPA) exert growth factor-like effects through specific G protein-coupled receptors. The presence of different LPA receptors often determines the signaling mechanisms and physiological consequences in environments. Among four members receptor family, LPA2 has been shown to be overexpressed colon cancer suggesting that by may potentiate survival tumor cells. In this study, we examined effect on cells using Caco-2 as a cell model system. rescued from apoptosis elicited chemotherapeutic drug, etoposide. This protection was accompanied abrogation etoposide-induced stimulation caspase activity via mechanism dependent Erk PI3K. contrast, perturbation cellular mediated knockdown scaffold protein NHERF2 abrogated protective LPA. Etoposide decreased expression Bcl-2, which reversed phosphorylation level proapoptotic Bad an Erk-dependent manner, without changing expression. We further show treatment resulted delayed activation Erk. These results indicate protects apoptotic insult involving Erk, Bad, Bcl-2.