Roles of lysophosphatidic acid (LPA) receptor-2 (LPA₂) in the regulation of cellular responses induced by X-ray irradiation and hydrogen peroxide in pancreatic cancer cells

PurposeLysophosphatidic acid (LPA) receptor-mediated signaling regulates various biological functions in cancer cells. This study aimed to evaluate the roles of LPA receptor-2 (LPA(2)) in cellular responses induced by X-ray irradiation in pancreatic cancer PANC-1 cells. Since X-ray irradiation generates reactive oxygen species (ROS), PANC-1 cells were treated with hydrogen peroxide (H2O2). H2O2 is a key member of ROS.MethodsTo investigate the cell survival rate to X-ray irradiation, PANC-1 cells were irradiated with X-rays (2.5-15 Gy). LPAR2 expression levels were measured by quantitative real-time RT-PCR analysis. The effects of LPA(2) on the cell survival and motility were evaluated using LPA(2) knockdown cells. To establish H2O2 treated cells, PANC-1 cells were cultured in 10% FBS-DMEM with H2O2 (30 & mu;M) for 2 weeks. The cell motility and survival rate to cisplatin (CDDP) of H2O2 treated cells were examined.ResultsLPAR2 expression was significantly increased in PANC-1 cells irradiated with X-rays. PANC-1 cell motility was markedly decreased by X-ray irradiation. The reduced cell motility activity by X-ray irradiation was enhanced by LPA(2) knockdown. The cell survival to X-ray irradiation was elevated in PANC-1 cells treated with GRI-977143 (LPA(2) agonist) and suppressed by LPA(2) knockdown. On the other hand, LPAR2 expression was markedly higher in H2O2 treated cells than in H2O2 untreated cells. H2O2 treated cells showed the high cell survival to CDDP in comparison with H2O2 untreated cells. GRI-977143 increased the cell survival to CDDP of H2O2 treated cells, while LPA(2) knockdown suppressed.ConclusionsThe present results suggest that the activation of LPA(2)-mediated signaling plays an important role in the modulation of cellular functions induced by X-ray irradiation and H2O2 in PANC-1 cells.