Lysophosphatidic acid (LPA) mediates a variety of biological functions via the binding of G protein-coupled LPA receptors (LPA receptor-1 (LPA1) to LPA6). This study aimed to investigate the roles of LPA2 and LPA3 in the modulation of chemoresistance to anticancer drug in lung cancer A549 cells. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 2 days. The cell survival rate to CDDP of A549 cells was significantly elevated by an LPA2 agonist, GRI-977143. To evaluate the roles of LPA2-mediated signaling in cell survival during tumor progression, highly migratory (A549-R10) cells were generated from A549 cells. In the presence of GRI-977143, the cell survival rate to CDDP of A549-R10 cells were markedly higher than that of A549 cells, correlating with LPAR2 expression level. Moreover, to assess the effects of long-term anticancer drug treatment on cell survival, the long-term CDDP treated (A549-CDDP) cells were established from A549 cells. The cell survival rate to CDDP of A549-CDDP cells was elevated by GRI-977143. Since LPAR3 expression level was significantly higher in A549-CDDP cells than in A549 cells, we investigated the roles of LPA3 in the cell survival to CDDP of A549 cells, using an LPA3 agonist, 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate ((2S)-OMPT). The cell survival rate to CDDP of A549 cells was significantly reduced by (2S)-OMPT treatment. In the presence of (2S)-OMPT, the cell survival rate to CDDP of A549 cells was elevated by LPA3 knockdown. These results suggest that LPA signaling via LPA2 and LPA3 is involved in the regulation of chemoresistance in A549 cells treated with CDDP.

中文翻译：

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溶血磷脂酸（LPA）受体2（LPA2）和LPA3对肺癌细胞抗癌药物化学抗性的调节作用。

溶血磷脂酸（LPA）通过G蛋白偶联的LPA受体（LPA受体1（LPA1）与LPA6）的结合来介导多种生物学功能。这项研究旨在调查LPA2和LPA3在肺癌A549细胞对抗癌药物的化学耐药性调节中的作用。在细胞存活测定中，每24小时用顺铂（CDDP）处理细胞2天。LPA2激动剂GRI-977143显着提高了A549细胞对CDDP的细胞存活率。为了评估LPA2介导的信号传导在肿瘤进展过程中的细胞存活中的作用，从A549细胞中产生了高度迁移的（A549-R10）细胞。在存在GRI-977143的情况下，A549-R10细胞对CDDP的细胞存活率明显高于A549细胞，与LPAR2表达水平相关。此外，为了评估长期抗癌药物治疗对细胞存活的影响，从A549细胞建立了长期CDDP处理（A549-CDDP）细胞。通过GRI-977143提高了A549-CDDP细胞对CDDP的细胞存活率。由于A549-CDDP细胞中LPAR3的表达水平显着高于A549细胞，因此我们使用LPA3激动剂1-油酰基-2-甲基-sn-甘油-酯来研究LPA3在A549细胞的CDDP存活中的作用。 3-磷酸​​硫代磷酸酯（（2S）-OMPT）。（2S）-OMPT处理显着降低了A549细胞对CDDP的细胞存活率。在（2S）-OMPT的存在下，通过LPA3敲低提高了A549细胞对CDDP的细胞存活率。这些结果表明，经由LPA2和LPA3的LPA信号传导参与了用CDDP处理的A549细胞中化学抗性的调节。