{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T20:55:09Z","timestamp":1774558509813,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Morphine is an opioid analgesic drug routinely used to treat pain in several medical conditions including cancer. Increasing evidence has shown that morphine can directly modulate cancer growth via regulating angiogenesis. In this work, we investigated the effect of morphine on angiogenesis under pathological conditions. We showed that morphine, in a concentration typical of that observed in patient's blood, stimulates tumour angiogenesis under serum deprivation and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced oxidative stress conditions. We found that morphine protected human lung tumour associated\u2010endothelial cell (HLT\u2010EC) against serum deprivation or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced inhibition of capillary network formation. Furthermore, morphine stimulated other biological functions of HLT\u2010EC under serum deprivation and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced pathological conditions, such as growth, migration and survival, without affecting HLT\u2010EC adhesion. Interestingly, morphine at the same concentration did not affect lung tumour cell growth and survival, suggesting the specific protective role of morphine at low micromolar concentrations on tumour angiogenesis. Using in vivo Matrigel angiogenesis assay, it was found that morphine stimulated in vivo angiogenesis under H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced pathological condition. The opioid receptor antagonist, naloxone, did not inhibit the protective activity of morphine in in vivo angiogenesis, indicating that the effect was less likely to be mediated by the typical opioid receptors. Mechanism analysis indicated that morphine alleviated serum deprivation and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced angiogenesis inhibition via reducing oxidative stress and damage, and activating Akt\/mTOR\/eIF4E signalling. We demonstrate the protective role of morphine on tumour angiogenesis under pathological conditions. Our work suggests that clinical use of morphine may be harmful in patients with angiogenesis\u2010dependent cancers.<\/jats:p>","DOI":"10.1111\/1440-1681.13191","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T07:26:18Z","timestamp":1571124378000},"page":"227-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Morphine stimulates angiogenesis through Akt\/mTOR\/eIF4E activation under serum deprivation or H<sub>2<\/sub>O<sub>2<\/sub>\u2010induced oxidative stress condition"],"prefix":"10.1111","volume":"47","author":[{"given":"Kun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Jingzhou Central Hospital The Second Clinical Medical College Yangtze University Jingzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Taihe Hospital Hubei University of Medicine Shiyan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First People\u2019s Hospital of Jingzhou The First Clinical Medical College Yangtze University Jingzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Jingzhou Central Hospital The Second Clinical Medical College Yangtze University Jingzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Jingzhou Central Hospital The Second Clinical Medical College Yangtze University Jingzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department 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