Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer Models by Targeting EGFR

Anticancer Res. 2017 Nov;37(11):6015-6023. doi: 10.21873/anticanres.12048.

Abstract

Background/aim: Omega 3 polyunsaturated fatty acids (PUFAs) have been shown to inhibit the induction and progression of many tumor types. The aim of this study was to determine the anticancer effect of docosahexaenoic acid monoglyceride (MAG-DHA) alone and in combination with the chemotherapeutic agent carboplatin (CBT) on lung cancer models.

Materials and methods: Adenocarcinoma cell lines A549 and H1299 were used to evaluate the effect of combined MAG-DHA and CBT treatments both in vitro and in vivo in xenograft models.

Results: MAG-DHA+CBT treatment decreased cell proliferation and invasion abilities of A549 and H1299 cells. Furthermore, MAG-DHA+CBT treatment resulted in a decreased activation of epithelial growth factor receptor (EGFR) and its downstream extracellular signal-regulated kinase (ERK) in cell lysates. In A549 and H1299 xenograft mouse models, MAG-DHA+CBT treatment reduced tumor growth.

Conclusion: Combined MAG-DHA and CBT treatment inhibited tumor growth by suppressing EGFR and ERK signaling pathways in lung carcinoma cells.

Keywords: DHA; EGFR; carboplatin; lung carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carboplatin / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Synergism*
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy*
  • Monoglycerides / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Monoglycerides
  • docosahexaenoic acid monoacylglyceride
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors