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

Purpose: Lysophosphatidic acid (LPA) receptor-mediated signaling regulates various biological functions in cancer cells. This study aimed to evaluate the roles of LPA receptor-2 (LPA) 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 (HO). HO is a key member of ROS.

Methods: To investigate the cell survival rate to X-ray irradiation, PANC-1 cells were irradiated with X-rays (2.5-15 Gy). expression levels were measured by quantitative real-time RT-PCR analysis. The effects of LPA on the cell survival and motility were evaluated using LPA knockdown cells. To establish HO treated cells, PANC-1 cells were cultured in 10% FBS-DMEM with HO (30 µM) for 2 weeks. The cell motility and survival rate to cisplatin (CDDP) of HO treated cells were examined.

Results: 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 knockdown. The cell survival to X-ray irradiation was elevated in PANC-1 cells treated with GRI-977143 (LPA agonist) and suppressed by LPA knockdown. On the other hand, expression was markedly higher in HO treated cells than in HO untreated cells. HO treated cells showed the high cell survival to CDDP in comparison with HO untreated cells. GRI-977143 increased the cell survival to CDDP of HO treated cells, while LPA knockdown suppressed.

Conclusions: The present results suggest that the activation of LPA-mediated signaling plays an important role in the modulation of cellular functions induced by X-ray irradiation and HO in PANC-1 cells.