Abstract Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits several biological functions by binding to G-protein-coupled LPA receptors (LPA receptor-1 (LPA1) to LPA6). The present study aimed to evaluate whether LPA signaling via LPA2 and LPA5 is involved in the chemoresistance to anticancer drugs in colon cancer DLD1 cells. In cell survival assay, cells were treated with fluorouracil (5-FU) every 24 h for 2 days. The cell survival rate to 5-FU of DLD1 cells was significantly decreased by LPA treatment. In the presence of LPA, the cell survival rate to 5-FU was significantly elevated by LPA5 knockdown. Before initiation of the cell survival assay, cells were pretreated with an LPA2 agonist, GRI-977143. The cell survival rate to 5-FU was markedly increased in DLD1 cells treated with GRI-977143. In the presence of GRI-977143, the elevated cell survival rate of DLD1 cells was reduced by LPA2 knockdown. To assess the effects of LPA2 and LPA5 on the enhancement of chemoresistance, long-term 5-FU treated (DLD-5FU) cells were generated from DLD1 cells. The cell survival rate to 5-FU of DLD-5FU cells were significantly elevated by LPA5 knockdown. GRI-977143 treatment increased the cell survival rate to 5-FU of DLD-5FU cells. These results suggest that LPA2 promotes and LPA5 suppresses the acquisition of chemoresistance in colon cancer cells treated with anticancer drugs.

中文翻译：

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溶血磷脂酸受体2（LPA2）和LPA5对结肠癌细胞耐药性调控的不同作用

摘要 溶血磷脂酸 (LPA) 是一种简单的生理脂质，通过与 G 蛋白偶联的 LPA 受体（LPA 受体-1 (LPA1) 到 LPA6）结合而表现出多种生物学功能。本研究旨在评估通过 LPA2 和 LPA5 的 LPA 信号传导是否参与结肠癌 DLD1 细胞对抗癌药物的化学抗性。在细胞存活试验中，每 24 小时用氟尿嘧啶 (5-FU) 处理细胞 2 天。LPA 处理显着降低了 DLD1 细胞对 5-FU 的细胞存活率。在存在 LPA 的情况下，LPA5 敲低显着提高了细胞对 5-FU 的存活率。在细胞存活试验开始之前，细胞用 LPA2 激动剂 GRI-977143 进行预处理。在用 GRI-977143 处理的 DLD1 细胞中，5-FU 的细胞存活率显着增加。在 GRI-977143 存在的情况下，LPA2 敲低降低了 DLD1 细胞升高的细胞存活率。为了评估 LPA2 和 LPA5 对增强化学抗性的影响，从 DLD1 细胞生成长期 5-FU 处理的 (DLD-5FU) 细胞。LPA5 敲低显着提高了 DLD-5FU 细胞对 5-FU 的细胞存活率。GRI-977143 处理将 DLD-5FU 细胞的细胞存活率提高到 5-FU。这些结果表明，在用抗癌药物治疗的结肠癌细胞中，LPA2 促进和 LPA5 抑制化学抗性的获得。LPA5 敲低显着提高了 DLD-5FU 细胞对 5-FU 的细胞存活率。GRI-977143 处理将 DLD-5FU 细胞的细胞存活率提高到 5-FU。这些结果表明，在用抗癌药物治疗的结肠癌细胞中，LPA2 促进和 LPA5 抑制化学抗性的获得。LPA5 敲低显着提高了 DLD-5FU 细胞对 5-FU 的细胞存活率。GRI-977143 处理将 DLD-5FU 细胞的细胞存活率提高到 5-FU。这些结果表明，在用抗癌药物治疗的结肠癌细胞中，LPA2 促进和 LPA5 抑制化学抗性的获得。