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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gupta K,Kshirsagar S,Chang L,Schwartz R,Law PY,Yee D,Hebbel RPsubject
Has Abstractpub_date
2002-08-01 00:00:00pages
4491-8issue
15eissn
0008-5472issn
1538-7445journal_volume
62pub_type
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