在肿瘤微环境中，癌细胞可以适应低营养和低氧的情况。溶血磷脂酸(LPA)受体介导的信号参与了癌细胞恶性特性的推动。在本研究中，为了研究LPA受体在胰腺癌PANC-1细胞在低糖和缺氧条件下调节细胞活力和对顺铂（CDDP）的生存作用的作用，细胞在21％和1％的氧气条件下分别在4500毫克/升高葡萄糖（HG）-DMEM，500毫克/升中等葡萄糖（MG）-DMEM和100毫克/升低葡萄糖（LG）-DMEM中培养。与HG-DMEM细胞相比，MG-DMEM和LG-DMEM中培养的细胞中LPAR1和LPAR2基因的表达水平显著提高。在MG-DMEM和LG-DMEM中培养的细胞的细胞活动性和对CDDP的生存率显著低于在HG-DMEM中培养的细胞。 LPA1敲低可增强细胞对CDDP的生存率，而LPA2敲低则可抑制细胞对CDDP的生存率。在缺氧条件（1％ O2）下，MG-DMEM和LG-DMEM中培养的细胞中LPAR1、LPAR2和LPAR3表达明显高于在HG-DMEM中培养的细胞中。与HG-DMEM相比，在MG-DMEM和LG-DMEM中培养的细胞对CDDP的生存率升高。LPA3敲低可降低细胞对CDDP的生存率。这些结果表明，LPA受体介导的信号参与了在缺氧条件下调节胰腺癌PANC-1细胞的恶性特性中。版权所有©2023 Elsevier Inc.。保留所有权利。

In tumor microenvironment, cancer cells can adapt to low conditions of nutrients and oxygen. Lysophosphatidic acid (LPA) receptor-mediated signaling is involved in the promotion of malignant properties in cancer cells. In the present study, to examine the roles of LPA receptors in the regulation of cell motility and survival to cisplatin (CDDP) of pancreatic cancer PANC-1 cells under glucose-deprived and hypoxic conditions, cells were cultured in 4500 mg/L high glucose (HG)-DMEM, 500 mg/L middle glucose (MG)-DMEM and 100 mg/L low glucose (LG)-DMEM at 21% and 1% O2. The expression levels of LPAR1 and LPAR2 genes in cells cultured in MG-DMEM and LG-DMEM were significantly elevated, compared with HG-DMEM cells. The cell motility and survival rate to CDDP of cells cultured in MG-DMEM and LG-DMEM were significantly lower than those of cells cultured in HG-DMEM. The cell survival to CDDP was enhanced by LPA1 knockdown and suppressed by LPA2 knockdown. Under hypoxic conditions (1% O2), LPAR1, LPAR2 and LPAR3 expressions were markedly higher in cells cultured in MG-DMEM and LG-DMEM than in cells cultured in HG-DMEM. The cell survival rates to CDDP of cells cultured in MG-DMEM and LG-DMEM were elevated in comparison with HG-DMEM. The cell survival to CDDP was reduced by LPA3 knockdown. These results suggest that LPA receptor-mediated signaling is involved in the regulation of malignant properties of PANC-1 cells under glucose-deprived and hypoxic conditions.Copyright © 2023 Elsevier Inc. All rights reserved.