Effects of LPA₁ and LPA₆ on the regulation of colony formation activity in colon cancer cells treated with anticancer drugs

Abstract

Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits a variety of cellular responses via the activation of G protein-coupled transmembrane LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). The aim of our study was to investigate effects of LPA receptors on soft agar colony formation in colon cancer cells treated with anticancer drugs. DLD1 cells were treated with fluorouracil (5-FU) or cisplatin (CDDP) for at least six months (DLD-5FU and DLD-CDDP cells, respectively). LPAR1 gene expression was markedly elevated in DLD-5FU cells. In contrast, DLD-CDDP cells showed the high expression of LPAR6 gene. In colony formation assay, DLD-5FU cells formed markedly large-sized colonies, while no colony formation was observed in DLD1 and DLD-CDDP cells. The large-sized colonies formed in DLD-5FU cells were suppressed by LPA₁ knockdown. In contrast, LPA₆ knockdown increased the size of colonies. In addition, DLD-5FU cells were further treated with CDDP for three months (DLD-C-F cells). DLD-CDDP cells were also treated with 5-FU (DLD-F-C cells). DLD-C-F cells formed large-sized colonies, but not DLD-F-C cells, correlating with LPAR1 and LPAR6 gene expression levels. These results suggest that LPA₁ and LPA₆ may regulate the colony formation activity in DLD1 cells treated with anticancer drugs.

Keywords:

• LPA receptor
• colony formation
• anticancer drug
• colon cancer cells

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by JSPS KAKENHI [Grant Number 24590493] and by grants from the Faculty of Science and Engineering, Kindai University.