Ishimoto Kaichi, Minami Akito, Minami Kanako, Ueda Nanami, Tsujiuchi Toshifumi
Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, Higashiosaka, Osaka, Japan.
J Recept Signal Transduct Res. 2021 Feb;41(1):93-98. doi: 10.1080/10799893.2020.1794002. Epub 2020 Jul 16.
Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits several biological functions by binding to G-protein-coupled LPA receptors (LPA receptor-1 (LPA) to LPA). The present study aimed to evaluate whether LPA signaling LPA and LPA 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 LPA knockdown. Before initiation of the cell survival assay, cells were pretreated with an LPA 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 LPA knockdown. To assess the effects of LPA and LPA 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 LPA knockdown. GRI-977143 treatment increased the cell survival rate to 5-FU of DLD-5FU cells. These results suggest that LPA promotes and LPA suppresses the acquisition of chemoresistance in colon cancer cells treated with anticancer drugs.
溶血磷脂酸（LPA）是一种简单的生理性脂质，通过与G蛋白偶联的LPA受体（从LPA受体-1（LPA1）到LPA6）结合发挥多种生物学功能。本研究旨在评估LPA信号通路中的LPA1和LPA3是否参与结肠癌DLD1细胞对抗癌药物的化疗耐药性。在细胞存活试验中，细胞每24小时用氟尿嘧啶（5-FU）处理2天。LPA处理显著降低了DLD1细胞对5-FU的细胞存活率。在存在LPA的情况下，LPA基因敲低显著提高了对5-FU的细胞存活率。在细胞存活试验开始前，细胞用LPA激动剂GRI-977143预处理。用GRI-977143处理的DLD1细胞对5-FU的细胞存活率显著增加。在存在GRI-977143的情况下，LPA基因敲低降低了DLD1细胞升高的细胞存活率。为了评估LPA1和LPA3对化疗耐药性增强的影响，从DLD1细胞中生成了长期5-FU处理的（DLD-5FU）细胞。LPA基因敲低显著提高了DLD-5FU细胞对5-FU的细胞存活率。GRI-977143处理增加了DLD-5FU细胞对5-FU的细胞存活率。这些结果表明，LPA1促进而LPA3抑制在用抗癌药物处理的结肠癌细胞中获得化疗耐药性。
