Different effects of lysophosphatidic acid receptor-2 (LPA2) and LPA5 on the regulation of chemoresistance in colon cancer cells

• Published in: Journal of receptors and signal transduction 2021-02, Vol.41 (1), p.93-98
• Main Authors: Ishimoto, Kaichi, Minami, Akito, Minami, Kanako, Ueda, Nanami, Tsujiuchi, Toshifumi
• Format: Article
• Language: English
• Subjects: anticancer drugs; chemoresistance; colon cancer cells; LPA5; lysophosphatidic acid
• ISSN: 1079-9893; 1532-4281
• DOI: 10.1080/10799893.2020.1794002

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 1 ) to LPA 6 ). The present study aimed to evaluate whether LPA signaling via LPA 2 and LPA 5 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 5 knockdown. Before initiation of the cell survival assay, cells were pretreated with an LPA 2 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 2 knockdown. To assess the effects of LPA 2 and LPA 5 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 5 knockdown. GRI-977143 treatment increased the cell survival rate to 5-FU of DLD-5FU cells. These results suggest that LPA 2 promotes and LPA 5 suppresses the acquisition of chemoresistance in colon cancer cells treated with anticancer drugs.