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Review Article
Morphine as a suspect of aiding the propagation of cancer cells
Yusom Shin
Kosin Medical Journal 2017;32(2):164-169.
Published online: January 19, 2017

Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, Busan, Korea

Corresponding Author: Yusom Shin, Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University,262, Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel:+82-51-990-6283 Fax:+82-51-254-2504 E-mail:
• Received: April 10, 2017   • Accepted: April 19, 2017

Copyright © 2017 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Controlling pain in cancer patients is important for several reasons including patient quality of life (QOL). In moderate-to-severe cancer-pain management, opioid analgesics are indispensable. Among these, morphine is the most representative. Unfortunately, many studies have shown that morphine is potentially associated with cancer growth, recurrence, and metastasis. Specifically, in animal as well as in vivo and in vitro studies, morphine has been demonstrated to have possibly positive effects on cancer progression. However, those effects have not yet been confirmed as entirely harmful, for several reasons: the results of animal and laboratory research have not been subjected to clinical trials; there are as yet no well-designed clinical studies, and indeed, some studies have shown that morphine can have negative, suppression effects on tumor growth. This review paper will present some of the data on the potentially positive relationships between morphine and cancer. It should not be forgotten, though, that such relationships remain controversial, and that pain itself promotes cancer progression.
  • 1.van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol 2007;18:1437–49.ArticlePubMed
  • 2.Haumann J, Joosten EB, Everdingen MH. Pain prevalence in cancer patients: status quo or opportunities for improvement? Curr Opin Support Palliat Care 2017.Article
  • 3.Candido KD, Kusper TM, Knezevic NN. New Cancer Pain Treatment Options. Curr Pain Headache Rep 2017;21:12.ArticlePubMed
  • 4.Vargas-Schaffer G. Is the WHO analgesic ladder still valid? Twenty-four years of experience. Can Fam Physician 2010;56:514–7.PubMedPMC
  • 5.Ma Y, Ren Z, Ma S, Yan W, He M, Wang D, et al. Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level. Ren Fail 2017;39:258–64.ArticlePubMed
  • 6.Bimonte S, Barbieri A, Rea D, Palma G, Luciano A, Cuomo A, et al. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression. Biomed Res Int 2015;2015:161508.ArticlePubMedPMC
  • 7.Nguyen J, Luk K, Vang D, Soto W, Vincent L, Robiner S, et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth 2014;113(Suppl 1):i4–13.ArticlePubMedPMC
  • 8.Vassou D, Notas G, Hatzoglou A, Castanas E, Kampa M. Opioids increase bladder cancer cell migration via bradykinin B2 receptors. Int J Oncol 2011;39:697–707.ArticlePubMed
  • 9.Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, et al. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer 2007;97:1523–31.ArticlePubMedPMC
  • 10.Sasamura T, Nakamura S, Iida Y, Fujii H, Murata J, Saiki I, et al. Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol 2002;441:185–91.ArticlePubMed
  • 11.Koodie L, Yuan H, Pumper JA, Yu H, Charboneau R, Ramkrishnan S, et al. Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. Am J Pathol 2014;184:1073–84.ArticlePubMedPMC
  • 12.Afsharimani B, Baran J, Watanabe S, Lindner D, Cabot PJ, Parat MO. Morphine and breast tumor metastasis: the role of matrix-degrading enzymes. Clin Exp Metastasis 2014;31:149–58.ArticlePubMed
  • 13.Li G, Low PS. Synthesis and evaluation of a ligand targeting the μ and δ opioid receptors for drug delivery to lung cancer. Bioorg Med Chem Lett 2017;27:2074–8.ArticlePubMed
  • 14.Lennon FE, Moss J, Singleton PA. The μ-opioid receptor in cancer progression: is there a direct effect? Anesthesiology 2012;116:940–5.PubMed
  • 15.Grandhi RK, Lee S, Abd-Elsayed A. Does Opioid Use Cause Angiogenesis and Metastasis? Pain Med 2017;18:140–51.ArticlePubMed
  • 16.Roy S, Ninkovic J, Banerjee S, Charboneau RG, Das S, Dutta R, et al. Opioid drug abuse and modu- lation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 2011;6:442–65.ArticlePubMedPMC
  • 17.Roy S, Wang J, Kelschenbach J, Koodie L, Martin J. Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol 2006;1:77–89.ArticlePubMed
  • 18.Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883–99.ArticlePubMedPMC
  • 19.Finley MJ, Happel CM, Kaminsky DE, Rogers TJ. Opioid and nociceptin receptors regulate cyto-kine and cytokine receptor expression. Cell Immunol 2008;252:146–54.ArticlePubMedPMC
  • 20.Lennon FE, Mirzapoiazova T, Mambetsariev B, Salgia R, Moss J, Singleton PA. Overexpression of the μ-opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis. Anesthesiology 2012;116:857–67.ArticlePubMed
  • 21.Gach K, Wyrębska A, Fichna J, Janecka A. The role of morphine in regulation of cancer cell growth. Naunyn Schmiedebergs Arch Pharmacol 2011;384:221–30.ArticlePubMedPMC
  • 22.Bortsov AV, Millikan RC, Belfer I, Boortz-Marx RL, Arora H, McLean SA. μ-Opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer. Anesthesiology 2012;116:896–902.ArticlePubMed
  • 23.Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004;21:137–48.ArticlePubMed
  • 24.Carr DJ, Rogers TJ, Weber RJ. The relevance of opioids and opioid receptors on immunocompetence and immune homeostasis. Proc Soc Exp Biol Med 1996;213:248–57.ArticlePubMed
  • 25.Wigmore T, Farquhar-Smith P. Opioids and cancer: friend or foe? Curr Opin Support Palliat Care 2016;10:109–18.PubMed
  • 26.Gong L, Dong C, Ouyang W, Qin Q. Regulatory T cells: a possible promising approach to cancer recurrence induced by morphine. Med Hypotheses 2013;80:308–10.ArticlePubMed
  • 27.Hua S, Cabot PJ. Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications. Trends Pharmacol Sci 2010;31:427–33.ArticlePubMed
  • 28.Yin D, Mufson RA, Wang R, Shi Y. Fas-mediated cell death promoted by opioids. Nature 1999;397:218.ArticlePubMed
  • 29.Hayashi T, Tsao LI, Su TP. Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells. Synapse 2002;43:86–94.ArticlePubMed
  • 30.Afsharimani B, Cabot P, Parat MO. Morphine and tumor growth and metastasis. Cancer Metastasis Rev 2011;30:225–38.ArticlePubMed
  • 31.Hatsukari I, Hitosugi N, Ohno R, Hashimoto K, Nakamura S, Satoh K, et al. Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res 2007;27:857–64.PubMed
  • 32.Singleton PA, Mambetsariev N, Lennon FE, Mathew B, Siegler JH, Moreno-Vinasco L, et al. Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors. J Angiogenes Res 2010;2:5.ArticlePubMedPMC

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        Morphine as a suspect of aiding the propagation of cancer cells
        Kosin Med J. 2017;32(2):164-169.   Published online January 19, 2017
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