{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:53:45Z","timestamp":1780329225051,"version":"3.54.1"},"reference-count":46,"publisher":"Pharmaceutical Society of Japan","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2020,5,1]]},"DOI":"10.1248\/bpb.b19-00779","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T22:07:27Z","timestamp":1588284447000},"page":"774-781","source":"Crossref","is-referenced-by-count":17,"title":["Morphine Stimulates Migration and Growth and Alleviates the Effects of Chemo Drugs &lt;i&gt;via&lt;\/i&gt; AMPK-Dependent Induction of Epithelial\u2013Mesenchymal Transition in Esophageal Carcinoma Cells"],"prefix":"10.1248","volume":"43","author":[{"given":"Jianfeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Central Hospital of Enshi Autonomous Prefecture"}],"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. <i>CA Cancer J. Clin.<\/i>, <b>66<\/b>, 115\u2013132 (2016).","DOI":"10.3322\/caac.21338"},{"key":"2","unstructured":"2) Stahl M, Budach W, Meyer HJ, Cervantes A. Esophageal cancer: clinical practice guidelines for diagnosis, treatment and follow-up. <i>Ann. Oncol.<\/i>, <b>21<\/b> (Suppl. 5), v46\u2013v49 (2010)."},{"key":"3","unstructured":"3) Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M. Review article: the role of the perioperative period in recurrence after cancer surgery. <i>Anesth. Analg.<\/i>, <b>110<\/b>, 1636\u20131643 (2010)."},{"key":"4","unstructured":"4) Oh TK, Jeon JH, Lee JM, Kim MS, Kim JH, Lim H, Kim SE, Eom W. Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes. <i>Dis. Esophagus<\/i>, <b>30<\/b>, 1\u20138 (2017)."},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Kelly E. Efficacy and ligand bias at the mu-opioid receptor. <i>Br. J. Pharmacol.<\/i>, <b>169<\/b>, 1430\u20131446 (2013).","DOI":"10.1111\/bph.12222"},{"key":"6","unstructured":"6) Rodr\u00edguez-Mu\u00f1oz M, Sanchez-Blazquez P, Vicente-Sanchez A, Berrocoso E, Garzon J. The mu-opioid receptor and the NMDA receptor associate in PAG neurons: implications in pain control. <i>Neuropsychopharmacology<\/i>, <b>37<\/b>, 338\u2013349 (2012)."},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) North WG, Liu F, Tian R, Abbasi H, Akerman B. NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines. <i>Clin. Pharmacol.<\/i>, <b>7<\/b>, 111\u2013117 (2015).","DOI":"10.2147\/CPAA.S90367"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Koodie L, Ramakrishnan S, Roy S. Morphine suppresses tumor angiogenesis through a HIF-1alpha\/p38MAPK pathway. <i>Am. J. Pathol.<\/i>, <b>177<\/b>, 984\u2013997 (2010).","DOI":"10.2353\/ajpath.2010.090621"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Koodie L, Yuan H, Pumper JA, Yu H, Charboneau R, Ramkrishnan S, Roy S. Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. <i>Am. J. Pathol.<\/i>, <b>184<\/b>, 1073\u20131084 (2014).","DOI":"10.1016\/j.ajpath.2013.12.019"},{"key":"10","unstructured":"10) Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, Hebbel RP. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. <i>Cancer Res.<\/i>, <b>62<\/b>, 4491\u20134498 (2002)."},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Bimonte S, Barbieri A, Rea D, Palma G, Luciano A, Cuomo A, Arra C, Izzo F. Morphine promotes tumor angiogenesis and increases breast cancer progression. <i>BioMed Res. Int.<\/i>, <b>2015<\/b>, 161508 (2015).","DOI":"10.1155\/2015\/161508"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Gach K, Wyrebska A, Fichna J, Janecka A. The role of morphine in regulation of cancer cell growth. <i>Naunyn Schmiedebergs Arch. Pharmacol.<\/i>, <b>384<\/b>, 221\u2013230 (2011).","DOI":"10.1007\/s00210-011-0672-4"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Niu DG, Peng F, Zhang W, Guan Z, Zhao HD, Li JL, Wang KL, Li TT, Zhang Y, Zheng FM, Xu F, Han QN, Gao P, Wen QP, Liu Q. Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer. <i>Oncotarget<\/i>, <b>6<\/b>, 3963\u20133976 (2015).","DOI":"10.18632\/oncotarget.2894"},{"key":"14","unstructured":"14) Boonstra JJ, Tilanus HW, Dinjens WN. Translational research on esophageal adenocarcinoma: from cell line to clinic. <i>Dis. Esophagus<\/i>, <b>28<\/b>, 90\u201396 (2015)."},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Kan T, Shimada Y, Sato F, Maeda M, Kawabe A, Kaganoi J, Itami A, Yamasaki S, Imamura M. Gene expression profiling in human esophageal cancers using cDNA microarray. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>286<\/b>, 792\u2013801 (2001).","DOI":"10.1006\/bbrc.2001.5400"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Boonstra JJ, van Marion R, Beer DG, Lin L, Chaves P, Ribeiro C, Pereira AD, Roque L, Darnton SJ, Altorki NK, Schrump DS, Klimstra DS, Tang LH, Eshleman JR, Alvarez H, Shimada Y, van Dekken H, Tilanus HW, Dinjens WN. Verification and unmasking of widely used human esophageal adenocarcinoma cell lines. <i>J. Natl. Cancer Inst.<\/i>, <b>102<\/b>, 271\u2013274 (2010).","DOI":"10.1093\/jnci\/djp499"},{"key":"17","unstructured":"17) Collins SL, Faura CC, Moore RA, McQuay HJ. Peak plasma concentrations after oral morphine: a systematic review. <i>J. Pain Symptom Manage.<\/i>, <b>16<\/b>, 388\u2013402 (1998)."},{"key":"18","unstructured":"18) Haga RB, Ridley AJ. Rho GTPases: regulation and roles in cancer cell biology. <i>Small GTPases<\/i>, <b>7<\/b>, 207\u2013221 (2016)."},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Yi BR, Kim TH, Kim YS, Choi KC. Alteration of epithelial\u2013mesenchymal transition markers in human normal ovaries and neoplastic ovarian cancers. <i>Int. J. Oncol.<\/i>, <b>46<\/b>, 272\u2013280 (2015).","DOI":"10.3892\/ijo.2014.2695"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Aburima A, Wraith KS, Raslan Z, Law R, Magwenzi S, Naseem KM. cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway. <i>Blood<\/i>, <b>122<\/b>, 3533\u20133545 (2013).","DOI":"10.1182\/blood-2013-03-487850"},{"key":"21","unstructured":"21) Giannoni E, Parri M, Chiarugi P. EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. <i>Antioxid. Redox Signal.<\/i>, <b>16<\/b>, 1248\u20131263 (2012)."},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Olianas MC, Concas D, Onali P. Agonist activity of naloxone benzoylhydrazone at recombinant and native opioid receptors. <i>Br. J. Pharmacol.<\/i>, <b>147<\/b>, 360\u2013370 (2006).","DOI":"10.1038\/sj.bjp.0706601"},{"key":"23","unstructured":"23) Dasgupta B, Seibel W. Compound C\/dorsomorphin: its use and misuse as an AMPK inhibitor. <i>Methods Mol. Biol.<\/i>, <b>1732<\/b>, 195\u2013202 (2018)."},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Kalghatgi S, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, Molina A, Shirihai OS, Collins JJ. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells. <i>Sci. Transl. Med.<\/i>, <b>5<\/b>, 192ra85 (2013).","DOI":"10.1126\/scitranslmed.3006055"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Rozenfeld-Granot G, Toren A, Amariglio N, Nagler A, Rosenthal E, Biniaminov M, Brok-Simoni F, Rechavi G. MAP kinase activation by mu opioid receptor in cord blood CD34(+)CD38(\u2212) cells. <i>Exp. Hematol.<\/i>, <b>30<\/b>, 473\u2013480 (2002).","DOI":"10.1016\/S0301-472X(02)00786-5"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Han SY, Jeong YJ, Choi Y, Hwang SK, Bae YS, Chang YC. Mitochondrial dysfunction induces the invasive phenotype, and cell migration and invasion, through the induction of AKT and AMPK pathways in lung cancer cells. <i>Int. J. Mol. Med.<\/i>, <b>42<\/b>, 1644\u20131652 (2018).","DOI":"10.3892\/ijmm.2018.3733"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. <i>J. Clin. Invest.<\/i>, <b>108<\/b>, 1167\u20131174 (2001).","DOI":"10.1172\/JCI13505"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Jin Q, Feng L, Behrens C, Bekele BN, Wistuba WK II, Hong WK, Lee HY. Hong, H.Y. Lee. Implication of AMP-activated protein kinase and Akt-regulated survivin in lung cancer chemopreventive activities of deguelin. <i>Cancer Res.<\/i>, <b>67<\/b>, 11630\u201311639 (2007).","DOI":"10.1158\/0008-5472.CAN-07-2401"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Park HU, Suy S, Danner M, Dailey V, Zhang Y, Li H, Hyduke DR, Collins BT, Gagnon G, Kallakury B, Kumar D, Brown ML, Fornace A, Dritschilo A, Collins SP. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. <i>Mol. Cancer Ther.<\/i>, <b>8<\/b>, 733\u2013741 (2009).","DOI":"10.1158\/1535-7163.MCT-08-0631"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Xu ZX, Liang J, Haridas V, Gaikwad A, Connolly FP, Mills GB, Gutterman JU. A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase. <i>Cell Death Differ.<\/i>, <b>14<\/b>, 1948\u20131957 (2007).","DOI":"10.1038\/sj.cdd.4402207"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Zhou W, Han WF, Landree LE, Thupari JN, Pinn ML, Bililign T, Kim EK, Vadlamudi A, Medghalchi SM, El Meskini R, Ronnett GV, Townsend CA, Kuhajda FP. Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells. <i>Cancer Res.<\/i>, <b>67<\/b>, 2964\u20132971 (2007).","DOI":"10.1158\/0008-5472.CAN-06-3439"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Langelueddecke C, Jakab M, Ketterl N, Lehner L, Hufnagl C, Schmidt S, Geibel JP, Fuerst J, Ritter M. Effect of the AMP-kinase modulators AICAR, metformin and compound C on insulin secretion of INS-1E rat insulinoma cells under standard cell culture conditions. <i>Cell. Physiol. Biochem.<\/i>, <b>29<\/b>, 75\u201386 (2012).","DOI":"10.1159\/000337589"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Nagumo H, Sasaki Y, Ono Y, Okamoto H, Seto M, Takuwa Y. Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells. <i>Am. J. Physiol. Cell Physiol.<\/i>, <b>278<\/b>, C57\u2013C65 (2000).","DOI":"10.1152\/ajpcell.2000.278.1.C57"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Cronin-Fenton D. Opioids and breast cancer recurrence. <i>Curr. Opin. Support. Palliat. Care<\/i>, <b>13<\/b>, 88\u201393 (2019).","DOI":"10.1097\/SPC.0000000000000426"},{"key":"35","unstructured":"35) Diaz-Cambronero O, Mazzinari G, Cata JP. Perioperative opioids and colorectal cancer recurrence: a systematic review of the literature. <i>Pain Manag<\/i>, <b>8<\/b>, 353\u2013361 (2018)."},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Juneja R. Opioids and cancer recurrence. <i>Curr. Opin. Support. Palliat. Care<\/i>, <b>8<\/b>, 91\u2013101 (2014).","DOI":"10.1097\/SPC.0000000000000056"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Ma Y, Ren Z, Ma S, Yan W, He M, Wang D, Ding P. Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level. <i>Ren. Fail.<\/i>, <b>39<\/b>, 258\u2013264 (2017).","DOI":"10.1080\/0886022X.2016.1256322"},{"key":"38","unstructured":"38) Harper P, Hald O, Lwaleed BA, Kyyaly A, Johnston D, Cooper AJ, Birch B. The impact of morphine treatment on bladder cancer cell proliferation and apoptosis: <i>in vitro<\/i> studies. <i>Exp. Oncol.<\/i>, <b>40<\/b>, 190\u2013193 (2018)."},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Cao LH, Li HT, Lin WQ, Tan HY, Xie L, Zhong ZJ, Zhou JH. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. <i>Sci. Rep.<\/i>, <b>6<\/b>, 18706 (2016).","DOI":"10.1038\/srep18706"},{"key":"40","unstructured":"40) Kim JY, Ahn HJ, Kim JK, Kim J, Lee SH, Chae HB. Morphine suppresses lung cancer cell proliferation through the interaction with opioid growth factor receptor: an <i>in vitro<\/i> and human lung tissue study. <i>Anesth. Analg.<\/i>, <b>123<\/b>, 1429\u20131436 (2016)."},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Nishiwada T, Kawaraguchi Y, Uemura K, Kawaguchi M. Morphine inhibits cell viability and growth <i>via<\/i> suppression of vascular endothelial growth factor in human oral cancer HSC-3 cells. <i>J. Anesth.<\/i>, <b>33<\/b>, 408\u2013415 (2019).","DOI":"10.1007\/s00540-019-02645-1"},{"key":"42","unstructured":"42) Ecimovic P, Murray D, Doran P, McDonald J, Lambert DG, Buggy DJ. Direct effect of morphine on breast cancer cell function <i>in vitro<\/i>: role of the NET1 gene. <i>Br. J. Anaesth.<\/i>, <b>107<\/b>, 916\u2013923 (2011)."},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Saxena M, Balaji SA, Deshpande N, Ranganathan S, Pillai DM, Hindupur SK, Rangarajan A. AMP-activated protein kinase promotes epithelial\u2013mesenchymal transition in cancer cells through Twist1 upregulation. <i>J. Cell Sci.<\/i>, <b>131<\/b>, jcs208314 (2018).","DOI":"10.1242\/jcs.208314"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Li L, Zhang H, Li T, Zhang B. Involvement of adenosine monophosphate-activated protein kinase in morphine-induced cardioprotection. <i>J. Surg. Res.<\/i>, <b>169<\/b>, 179\u2013187 (2011).","DOI":"10.1016\/j.jss.2009.11.007"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Asiedu MN, Dussor G, Price TJ. Targeting AMPK for the alleviation of pathological pain. <i>Exp. Suppl.<\/i>, <b>107<\/b>, 257\u2013285 (2016).","DOI":"10.1007\/978-3-319-43589-3_11"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46) Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. <i>Nat. Cell Biol.<\/i>, <b>13<\/b>, 1016\u20131023 (2011).","DOI":"10.1038\/ncb2329"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/5\/43_b19-00779\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T06:33:45Z","timestamp":1588833225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/5\/43_b19-00779\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b19-00779","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,1]]}}}