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.
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