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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 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 (H 2 O 2 ). H 2 O 2  is a key member of ROS. To 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 H 2 O 2  treated cells, PANC-1 cells were cultured in 10% FBS-DMEM with H 2 O 2  (30 µM) for 2 weeks. The cell motility and survival rate to cisplatin (CDDP) of H 2 O 2  treated cells were examined. LPAR2  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 H 2 O 2  treated cells than in H 2 O 2  untreated cells. H 2 O 2  treated cells showed the high cell survival to CDDP in comparison with H 2 O 2  untreated cells. GRI-977143 increased the cell survival to CDDP of H 2 O 2  treated cells, while LPA 2  knockdown suppressed. The 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 H 2 O 2  in PANC-1 cells.

international journal of radiation biology

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