Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells.
Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells.
复制标题
DOI：
10.1016/j.cellsig.2020.109551
复制
发表时间：
2020-01
影响因子：
4.8
通讯作者：
N. Ueda;Kanako Minami;Kaichi Ishimoto;T. Tsujiuchi
中科院分区：
文献类型：
--
作者：
N. Ueda;Kanako Minami;Kaichi Ishimoto;T. Tsujiuchi
溶血磷脂酸（LPA）通过G蛋白偶联LPA受体（LPA receptor-1 (LPA1) to LPA6）的结合介导多种生物学功能。本研究旨在探讨lpa2和lpa3在肺癌A549细胞化疗耐药调控中的作用。在细胞存活试验中，每24 h用顺铂（CDDP）处理细胞2天。lpa2激动剂GRI-977143可显著提高A549细胞对CDDP的存活率。为了评估lpa2介导的信号在肿瘤进展过程中细胞存活中的作用，我们从A549细胞中产生了高迁移（A549- r10）细胞。在GRI-977143存在的情况下，A549- r10细胞对CDDP的存活率明显高于A549细胞，这与lpar2的表达水平有关。此外，为了评估长期抗癌药物治疗对细胞存活的影响，我们从A549细胞中建立了长期CDDP处理（A549-CDDP）细胞。GRI-977143可提高A549-CDDP细胞对CDDP的存活率。由于elpar3在A549-CDDP细胞中的表达水平明显高于A549细胞，我们使用lpa3激动剂1-油基-2-甲基-森-甘油-3-磷酸硫酸盐（(2S)-OMPT）研究了lpa3在A549细胞对CDDP细胞存活中的作用。（2S）-OMPT处理显著降低A549细胞对CDDP的存活率。在(2S)-OMPT存在下，敲低lpa3可提高A549细胞对CDDP的存活率。这些结果表明，LPA信号通过lpa2和lpa3参与了CDDP处理A549细胞的化疗耐药调控。
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 LPA2and LPA3in 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 LPA2agonist, 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 withLPAR2expression 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. SinceLPAR3expression level was significantly higher in A549-CDDP cells than in A549 cells, we investigated the roles of LPA3in the cell survival to CDDP of A549 cells, using an LPA3agonist, 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 LPA3knockdown. These results suggest that LPA signaling via LPA2and LPA3is involved in the regulation of chemoresistance in A549 cells treated with CDDP.