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首页> 外文期刊>Cellular Signalling >Effects of lysophosphatidic acid (LPA) receptor-2 (LPA(2)) and LPA(3) on the regulation of chemoresistance to anticancer drug in lung cancer cells
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Effects of lysophosphatidic acid (LPA) receptor-2 (LPA(2)) and LPA(3) on the regulation of chemoresistance to anticancer drug in lung cancer cells

机译：溶血磷脂酸（LPA）受体-2（LPA）受体-2和LPA（3）对肺癌细胞抗癌药物调节的影响

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Lysophosphatidic acid (LPA) mediates a variety of biological functions via the binding of G protein-coupled LPA receptors (LPA receptor-1 (LPA(1)) to LPA(6)). This study aimed to investigate the roles of LPA(2) and LPA(3) 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 LPA 2 agonist, GRI-977143. To evaluate the roles of LPA 2 -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 LPAR(2) 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 LPAR(3) expression level was significantly higher in A549-CDDP cells than in A549 cells, we investigated the roles of LPA(3) in the cell survival to CDDP of A549 cells, using an LPA(3) 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 LPA(3) knockdown. These results suggest that LPA signaling via LPA(2) and LPA(3) is involved in the regulation of chemoresistance in A549 cells treated with CDDP.
机译：溶血磷脂酸（LPA）通过G蛋白偶联的LPA受体（LPA受体-1（LPA（1））至LPA（6））的结合介导各种生物学功能。该研究旨在探讨LPA（2）和LPA（3）在肺癌A549细胞中对抗癌药物调节的作用。在细胞存活测定中，每24小时用顺铂（CDDP）处理细胞2天。通过LPA 2激动剂GRI-977143，CELT至A549细胞CDDP的细胞存活率显着升高。为了评估肿瘤进展期间细胞存活中LPA 2介导的信号传导的作用，从A549细胞产生高度迁移（A549-R10）细胞。在GRI-977143的存在下，A549-R10细胞CDDP的细胞存活率明显高于A549细胞的CDDP，与LPAR（2）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升高了A549-CDDP细胞CDDP的细胞存活率。由于A549-CDDP细胞中的LPAR（3）表达水平明显高于A549细胞，因此使用LPA（3）激动剂1-OXEORL -2-甲基-Sn-甘油-3-磷酸酯（（2S）-OmPT）。通过（2S）-OMPT处理显着降低了A549细胞CDDP的细胞存活率。在（2S）-OmPT的存在下，通过LPA（3）敲低升高A549细胞CDDP的细胞存活率。这些结果表明，通过LPA（2）和LPA（3）的LPA信号传导参与用CDD处理的A549细胞中的化学抑制性调节。

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