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Morphine-induced epidermal growth factor pathway activation in non-small cell lung cancer

Naomi Fujioka1, Julia Nguyen, Chunsheng Chen

  • 1Department of Medicine, Division of Hematology, Oncology, Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.

Anesthesia and Analgesia
|October 18, 2011
PubMed
Abstract

Insights

Morphine activates opioid receptors (ORs) to coactivate epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC) cells. This coactivation promotes cancer cell proliferation and invasion, suggesting morphine may enhance lung cancer growth.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR) is coactivated by the micro-opioid receptor (MOR) in non-small cell lung cancer (NSCLC).
  • Opioid analgesics, as MOR agonists, may coactivate EGFR, promoting cancer cell growth and survival.

Purpose of the Study:

  • To investigate if clinically used opioid analgesics coactivate EGFR in NSCLC.
  • To determine the downstream signaling pathways and functional consequences of this coactivation.

Main Methods:

  • Utilized NSCLC cell line (H2009) with constitutive EGFR phosphorylation.
  • Employed Western immunoblotting, cytokine assays, immunofluorescence, proliferation, and invasion assays.
  • Examined the effects of morphine, opioid antagonists (naloxone), and EGFR inhibitors (erlotinib).

Main Results:

  • Morphine stimulated EGFR, Akt, and MAPK/ERK phosphorylation, similar to EGF.
  • Naloxone, erlotinib, and receptor silencing abrogated morphine- and EGF-induced signaling.
  • Morphine and EGF increased H2009 cell proliferation and invasion, effects reduced by naloxone and erlotinib.
  • Coexpression of MOR and EGFR was observed in human NSCLC tissue.

Conclusions:

  • Morphine-induced EGFR phosphorylation occurs via ORs, activating downstream signaling pathways.
  • Opioid receptors are involved in EGF-induced EGFR phosphorylation.
  • Morphine may promote lung cancer growth and invasion through EGFR coactivation.

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