{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:53:44Z","timestamp":1780329224111,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014901","name":"Hubei University of Arts and Science","doi-asserted-by":"publisher","award":["SJ166K"],"award-info":[{"award-number":["SJ166K"]}],"id":[{"id":"10.13039\/501100014901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Morphine is frequently applied in cancer patients for pain management. However, its effects on cancer are not well understood but observed to be specific to certain cancer types. We previously revealed the stimulatory properties of morphine in esophageal carcinoma. This work addressed the effects of morphine and its underlying mechanisms in cervical cancer. Proliferation, apoptosis, and migration assays were performed to examine the effects of morphine alone and its combinatory effects with chemotherapeutic drugs. Immunoblotting and biochemical analysis were performed to determine the underlying mechanisms of morphine's action. Morphine promoted proliferation in opioid receptor\u2010dependent manner and stimulated migration in opioid receptor\u2010independent manner. However, morphine did not affect cervical cancer cell survival. Morphine also interfered with all tested chemotherapeutic drugs (e.g., cisplatin, 5\u2010FU, and paclitaxel) and alleviates their efficacy. Mechanistically, morphine\u2010stimulated growth via activating EGFR\u2010mediated signaling pathways and is opioid\u2010receptor\u2010dependent; morphine\u2010stimulated migration via activating RhoA\u2010mediated signaling pathways and this is opioid receptor\u2010independent. Our work suggests a strong correlation of this opioid receptor on growth factor signaling to stimulate growth and opioid receptor\u2010independent activation of RhoA and consequent migration. Our findings have the potential to guide the clinical use of morphine for patients with cervical cancer.<\/jats:p>","DOI":"10.1002\/prp2.1016","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T13:25:03Z","timestamp":1665062703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Morphine stimulates cervical cancer cells and alleviates cytotoxicity of chemotherapeutic drugs via opioid receptor\u2010dependent and \u2010independent mechanisms"],"prefix":"10.1002","volume":"10","author":[{"given":"Zhengwen","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-1079","authenticated-orcid":false,"given":"Zhibao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang Hubei Province 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