Diverse effects of G-protein-coupled free fatty acid receptors on the regulation of cellular functions in lung cancer cells

Exp Cell Res. 2016 Mar 15;342(2):193-9. doi: 10.1016/j.yexcr.2016.03.008. Epub 2016 Mar 8.

Abstract

Free fatty acids (FFAs) are dietary nutrients which mediate a variety of biological effects through binding to G-protein-coupled FFA receptors (FFARs). G-protein-coupled receptor 120 (GPR120) and GPR40 are identified as FFARs for long- and medium-chain fatty acids. Here we investigated whether GPR120 and GPR40 are involved in the acquisition of malignant properties in lung cancer cells. Three lung cancer RLCNR, LL/2 and A549 cells used in this study expressed GPR120 and GPR40 genes. The cell motile activities of all cells were significantly suppressed by a GPR40 antagonist GW1100. In addition, GPR40 knockdown inhibited the cell motile activity of A549 cells. In gelatin zymography, matrix metalloproteinase-2 (MMP-2) activity in GPR40 knockdown was significantly lower than that in control cells. Next, to evaluate effects of GPR120 and GPR40 on cellular functions induced by anti-cancer drug, the long-term cisplatin (CDDP) treated (A549-CDDP) cells were generated. The expression levels of GPR120 and GPR40 were significantly decreased in A549-CDDP cells. While A549-CDDP cells showed the high cell motile activity, GW1100 suppressed the cell motile activity of A549-CDDP cells. These results demonstrate that GPR120 negatively and GPR40 positively regulate cellular functions during tumor progression in lung cancer cells.

Keywords: Cell motility; GPR120; GPR40; Invasion; Lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Benzoates / pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Endothelial Cells / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Methylamines / pharmacology
  • Mice
  • Propionates / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / physiology*

Substances

  • Antineoplastic Agents
  • Benzoates
  • FFAR1 protein, human
  • FFAR4 protein, human
  • GW1100
  • GW9508
  • Methylamines
  • Propionates
  • Pyrimidines
  • Receptors, G-Protein-Coupled
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Cisplatin