Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Academic Article uri icon

Overview

abstract

  • Morphine is used to treat pain in several medical conditions including cancer. Here we show that morphine, in a concentration typical of that observed in patients' blood, stimulates human microvascular endothelial cell proliferation and angiogenesis in vitro and in vivo. It does so by activating mitogen-activated protein kinase/extracellular signal-regulated kinase phosphorylation via Gi/Go-coupled G protein receptors and nitric oxide in these microvascular endothelial cells. Other contributing effects of morphine include activation of the survival signal PKB/Akt, inhibition of apoptosis, and promotion of cell cycle progression by increasing cyclin D1. Consistent with these effects, morphine in clinically relevant doses promotes tumor neovascularization in a human breast tumor xenograft model in mice leading to increased tumor progression. These results indicate that clinical use of morphine could potentially be harmful in patients with angiogenesis-dependent cancers.

publication date

  • August 1, 2002

Research

keywords

  • Analgesics, Opioid
  • Breast Neoplasms
  • MAP Kinase Signaling System
  • Morphine
  • Neovascularization, Physiologic
  • Protein Serine-Threonine Kinases

Identity

Scopus Document Identifier

  • 0036682055

PubMed ID

  • 12154060

Additional Document Info

volume

  • 62

issue

  • 15