Skip to main content

Advertisement

Log in

Opioid Analgesic Agents and Cancer Cell Biology

  • Cancer Anesthesia (B Riedel, Section Editor)
  • Published:
Current Anesthesiology Reports Aims and scope Submit manuscript

Abstract

There is growing interest in the notion that perioperative factors may influence the long-term outcome of cancer surgery. Among these factors, pharmacologic agents including anesthetics and analgesics have been scrutinized for their potential effect on tumors. Opioids are particularly interesting in this context, as conflicting literature reports both pro- and anti-tumor effects for this class of drugs in every aspect of tumor growth and metastasis that has been examined. Cancer and non-cancer cells important to the tumor biology may be affected, as demonstrated using a variety of in vitro and preclinical models. More evidence is required to optimize the perioperative pain management of cancer surgery patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Afsharimani B, Cabot PJ, Parat MO. Morphine use in cancer surgery. Front Pharmacol. 2011;2:46.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Afsharimani B, Cabot P, Parat MO. Morphine and tumor growth and metastasis. Cancer Metastasis Rev. 2011;30(2):225–38.

    Article  CAS  PubMed  Google Scholar 

  3. Lazarczyk M, Matyja E, Lipkowski AW. A comparative study of morphine stimulation and biphalin inhibition of human glioblastoma T98G cell proliferation in vitro. Peptides. 2010;31(8):1606–12.

    Article  CAS  PubMed  Google Scholar 

  4. Tegeder I, Grosch S, Schmidtko A, Haussler A, Schmidt H, Niederberger E, Scholich K, Geisslinger G. G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: involvement of p53 phosphorylation. Cancer Res. 2003;63(8):1846–52.

    CAS  PubMed  Google Scholar 

  5. Sueoka N, Sueoka E, Okabe S, Fujiki H. Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mrna expression. Carcinogenesis. 1996;17(11):2337–41.

    Article  CAS  PubMed  Google Scholar 

  6. Gach K, Szemraj J, Fichna J, Piestrzeniewicz M, Delbro DS, Janecka A. The influence of opioids on urokinase plasminogen activator on protein and mrna level in MCF-7 breast cancer cell line. Chem Biol Drug Des. 2009;74(4):390–6.

    Article  CAS  PubMed  Google Scholar 

  7. Nylund G, Pettersson A, Bengtsson C, Khorram-Manesh A, Nordgren S, Delbro DS. Functional expression of mu-opioid receptors in the human colon cancer cell line, HT-29, and their localization in human colon. Dig Dis Sci. 2008;53(2):461–6.

    Article  CAS  PubMed  Google Scholar 

  8. Janecka A, Fichna J, Kosson P, Zalewska-Kaszubska J, Krajewska U, Mirowski M, Rozalski M. Binding of the new morphiceptin analogs to human MCF-7 breast cancer cells and their effect on growth. Regul Pept. 2004;120(1–3):237–41.

    Article  CAS  PubMed  Google Scholar 

  9. Bohn LM, Belcheva MM, Coscia CJ. Mu-opioid agonist inhibition of kappa-opioid receptor-stimulated extracellular signal-regulated kinase phosphorylation is dynamin-dependent in C6 glioma cells. J Neurochem. 2000;74(2):574–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    Article  CAS  PubMed  Google Scholar 

  11. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407(6805):770–6.

    Article  CAS  PubMed  Google Scholar 

  12. Hsiao PN, Chang MC, Cheng WF, Chen CA, Lin HW, Hsieh CY, Sun WZ. Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways. Toxicology. 2009;256(1–2):83–91.

    Article  CAS  PubMed  Google Scholar 

  13. Kapasi AA, Coscia SA, Pandya MP, Singhal PC. Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte apoptosis by disparate ways. J Neuroimmunol. 2004;148(1–2):86–96.

    Article  CAS  PubMed  Google Scholar 

  14. Hatsukari I, Hitosugi N, Ohno R, Hashimoto K, Nakamura S, Satoh K, Nagasaka H, Matsumoto I, Sakagami H. Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res. 2007;27(2):857–64.

    CAS  PubMed  Google Scholar 

  15. Kugawa F, Matsumoto K, Aoki M. Apoptosis-like cell death of human breast cancer cell line MCF-7 induced by buprenorphine hydrochloride. Life Sci. 2004;75(3):287–99.

    Article  CAS  PubMed  Google Scholar 

  16. Qin Y, Li L, Chen J, Tang X, Liao C, Xie Y, Xiao Q. Fentanyl inhibits progression of human gastric cancer MGC-803 cells by NF-kappaB downregulation and pten upregulation in vitro. Oncol Res. 2012;20(2–3):61–9.

    Article  CAS  PubMed  Google Scholar 

  17. Lin X, Wang YJ, Li Q, Hou YY, Hong MH, Cao YL, Chi ZQ, Liu JG. Chronic high-dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway. FEBS J. 2009;276(7):2022–36.

    Article  CAS  PubMed  Google Scholar 

  18. Qin Y, Chen J, Li L, Liao CJ, Liang YB, Guan EJ, Xie YB. Exogenous morphine inhibits human gastric cancer MGC- 803 cell growth by cell cycle arrest and apoptosis induction. Asian Pac J Cancer Prev. 2012;13(4):1377–82.

    Article  PubMed  Google Scholar 

  19. Friesen C, Bacher S, Hormann I, Roscher M, Miltner E. Cytotoxic effects of opioids on cancer cell lines. Int J Clin Pharmacol Ther. 2011;49(1):60–2.

    CAS  PubMed  Google Scholar 

  20. Lu J, Liu Z, Zhao L, Tian H, Liu X, Yuan C. In vivo and in vitro inhibition of human liver cancer progress by downregulation of the μ-opioid receptor and relevant mechanisms. Oncol Rep. 2013;30(4):1731–8.

    Article  CAS  PubMed  Google Scholar 

  21. Zhao L, Zhu Y, Wang D, Chen M, Gao P, Xiao W, Rao G, Wang X, Jin H, Xu L, Sui N, et al. Morphine induces beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus. Autophagy. 2010;6(3):386–94.

    Article  CAS  PubMed  Google Scholar 

  22. 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. Cancer Res. 2002;62(15):4491–8.

    CAS  PubMed  Google Scholar 

  23. Iglesias M, Segura MF, Comella JX, Olmos G. Mu-opioid receptor activation prevents apoptosis following serum withdrawal in differentiated SH-SY5Y cells and cortical neurons via phosphatidylinositol 3-kinase. Neuropharmacology. 2003;44(4):482–92.

    Article  CAS  PubMed  Google Scholar 

  24. Lin X, Li Q, Wang YJ, Ju YW, Chi ZQ, Wang MW, Liu JG. Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappab transcriptional activation in neuroblastoma SH-SY5Y cells. Biochem J. 2007;406(2):215–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jiang X, Overholtzer M, Thompson CB. Autophagy in cellular metabolism and cancer. J Clin Invest. 2015;125(1):47–54.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Takeuchi R, Hoshijima H, Nagasaka H, Chowdhury SA, Kikuchi H, Kanda Y, Kunii S, Kawase M, Sakagami H. Induction of non-apoptotic cell death by morphinone in human promyelocytic leukemia HL-60 cells. Anticancer Res. 2006;26(5A):3343–8.

    CAS  PubMed  Google Scholar 

  27. Harimaya Y, Koizumi K, Andoh T, Nojima H, Kuraishi Y, Saiki I. Potential ability of morphine to inhibit the adhesion, invasion and metastasis of metastatic colon 26-L5 carcinoma cells. Cancer Lett. 2002;187(1–2):121–7.

    Article  CAS  PubMed  Google Scholar 

  28. Ecimovic P, Murray D, Doran P, McDonald J, Lambert DG, Buggy DJ. Direct effect of morphine on breast cancer cell function in vitro: role of the NET1 gene. Br J Anaesth. 2011;107(6):916–23.

    Article  CAS  PubMed  Google Scholar 

  29. 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(3):697–707.

    CAS  PubMed  Google Scholar 

  30. Duffy MJ, Duggan C. The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer. Clin Biochem. 2004;37(7):541–8.

    Article  CAS  PubMed  Google Scholar 

  31. Mignatti P, Rifkin DB. Nonenzymatic interactions between proteinases and the cell surface: novel roles in normal and malignant cell physiology. Adv Cancer Res. 2000;78:103–57.

    Article  CAS  PubMed  Google Scholar 

  32. Gach K, Szemraj J, Wyrebska A, Janecka A. The influence of opioids on matrix metalloproteinase-2 and -9 secretion and mrna levels in MCF-7 breast cancer cell line. Mol Biol Rep. 2011;38(2):1231–6.

    Article  CAS  PubMed  Google Scholar 

  33. 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(2):149–58.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang YF, Xu QX, Liao LD, Xu XE, Wu JY, Shen J, Wu ZY, Shen JH, Li EM, Xu LY. Kappa-opioid receptor in the nucleus is a novel prognostic factor of esophageal squamous cell carcinoma. Hum Pathol. 2013;44(9):1756–65.

    Article  CAS  PubMed  Google Scholar 

  35. Schreiber G, Campa MJ, Prabhakar S, O’Briant K, Bepler G, Patz EF Jr. Molecular characterization of the human delta opioid receptor in lung cancer. Anticancer Res. 1998;18(3A):1787–92.

    CAS  PubMed  Google Scholar 

  36. Bidlack JM. Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol. 2000;7(5):719–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS. Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation. J Biol Chem. 1995;270(51):30290–3.

    Article  CAS  PubMed  Google Scholar 

  38. Maneckjee R, Biswas R, Vonderhaar BK. Binding of opioids to human MCF-7 breast cancer cells and their effects on growth. Cancer Res. 1990;50(8):2234–8.

    CAS  PubMed  Google Scholar 

  39. Singleton PA, Mirzapoiazova T, Hasina R, Salgia R, Moss J. Increased mu-opioid receptor expression in metastatic lung cancer. Br J Anaesth. 2014;113(Suppl 1):i103–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zylla D, Gourley BL, Vang D, Jackson S, Boatman S, Lindgren B, Kuskowski MA, Le C, Gupta K, Gupta P. Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer. Cancer. 2013;119(23):4103–10.

    Article  CAS  PubMed  Google Scholar 

  41. Kasai S, Ikeda K. Pharmacogenomics of the human micro-opioid receptor. Pharmacogenomics. 2011;12(9):1305–20.

    Article  CAS  PubMed  Google Scholar 

  42. Bortsov AV, Millikan RC, Belfer I, Boortz-Marx RL, Arora H, McLean SA. Mu-opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer. Anesthesiology. 2012;116(4):896–902.

    Article  CAS  PubMed  Google Scholar 

  43. Wang S, Li Y, Liu XD, Zhao CX, Yang KQ. Polymorphism of A118G in μ-opioid receptor gene is associated with risk of esophageal squamous cell carcinoma in a chinese population. Int J Clin Oncol. 2013;18(4):666–9.

    Article  CAS  PubMed  Google Scholar 

  44. Cieslinska A, Sienkiewicz-Szlapka E, Kostyra E, Fiedorowicz E, Snarska J, Wronski K, Tenderenda M, Jarmolowska B, Matysiewicz M. μ-opioid receptor gene (OPRM1) polymorphism in patients with breast cancer. Tumour Biol. 2015. doi:https://doi.org/10.1007/s13277-015-3113-z.

  45. •• Wang X, Loram LC, Ramos K, de Jesus AJ, Thomas J, Cheng K, Reddy A, Somogyi AA, Hutchinson MR, Watkins LR, Yin H. Morphine activates neuroinflammation in a manner parallel to endotoxin. Proc Natl Acad Sci USA. 2012;109(16):6325–30. This article reports that morphine can cause TLR4 activation. This discovery has opened up novel research hypotheses in the context of opioids and cancer.

  46. Molteni M, Marabella D, Orlandi C, Rossetti C. Melanoma cell lines are responsive in vitro to lipopolysaccharide and express TLR-4. Cancer Lett. 2006;235(1):75–83.

    Article  CAS  PubMed  Google Scholar 

  47. Hassan F, Islam S, Tumurkhuu G, Naiki Y, Koide N, Mori I, Yoshida T, Yokochi T. Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide. BMC Cancer. 2006;6:281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tang XY, Zhu YQ, Wei B, Wang H. Expression and functional research of TLR4 in human colon carcinoma. Am J Med Sci. 2010;339(4):319–26.

    Article  PubMed  Google Scholar 

  49. Yang H, Wang B, Wang T, Xu L, He C, Wen H, Yan J, Su H, Zhu X. Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis. PLoS One. 2014;9(10):e109980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Brown JN, Ortiz GM, Angel TE, Jacobs JM, Gritsenko M, Chan EY, Purdy DE, Murnane RD, Larsen K, Palermo RE, Shukla AK, et al. Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels. Mol Cell Proteomics. 2012;11(9):605–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Koodie L, Roy S. Morphine and immunosuppression in the context of tumor growth and metastasis. In: Morphine and metastasis. Dordrecht: Springer; 2013. p 31–46.

  52. •• Horowitz M, Neeman E, Sharon E, Ben-Eliyahu S. Exploiting the critical perioperative period to improve long-term cancer outcomes. Nat Rev Clin Oncol. 2015;12(4):213–26. Comprehensive review on the various factors amenable to intervention in the perioperative period.

  53. Sacerdote P, Bianchi M, Gaspani L, Panerai AE. Effects of tramadol and its enantiomers on concanavalin-a induced-proliferation and NK activity of mouse splenocytes: involvement of serotonin. Int J Immunopharmacol. 1999;21(11):727–34.

    Article  CAS  PubMed  Google Scholar 

  54. Gaspani L, Bianchi M, Limiroli E, Panerai AE, Sacerdote P. The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats. J Neuroimmunol. 2002;129(1–2):18–24.

    Article  CAS  PubMed  Google Scholar 

  55. Sacerdote P, Bianchi M, Gaspani L, Manfredi B, Maucione A, Terno G, Ammatuna M, Panerai AE. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth Analg. 2000;90(6):1411–4.

    Article  CAS  PubMed  Google Scholar 

  56. Wang ZY, Wang CQ, Yang JJ, Sun J, Huang YH, Tang QF, Qian YN. Which has the least immunity depression during postoperative analgesia–morphine, tramadol, or tramadol with lornoxicam? Clin Chim Acta. 2006;369(1):40–5.

    Article  CAS  PubMed  Google Scholar 

  57. Zhou LW, Ding HL, Li MQ, Jin S, Wang XS, Ji LJ. Effect of tramadol on perioperative immune function in patients undergoing gastric cancer surgeries. Anesth Essays Res. 2013;7(1):54–7.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Boland JW, Foulds GA, Ahmedzai SH, Pockley AG. A preliminary evaluation of the effects of opioids on innate and adaptive human in vitro immune function. BMJ Support Palliat Care. 2014;4(4):357–67.

    Article  PubMed  Google Scholar 

  59. Beilin B, Grinevich G, Yardeni IZ, Bessler H. Tramadol does not impair the phagocytic capacity of human peripheral blood cells. Can J Anaesth. 2005;52(10):1035–9.

    Article  PubMed  Google Scholar 

  60. Fuggetta MP, Di Francesco P, Falchetti R, Cottarelli A, Rossi L, Tricarico M, Lanzilli G. Effect of morphine on cell-mediated immune responses of human lymphocytes against allogeneic malignant cells. J Exp Clin Cancer Res. 2005;24(2):255–63.

    CAS  PubMed  Google Scholar 

  61. Maneckjee R, Minna JD. Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ. 1994;5(10):1033–40.

    CAS  PubMed  Google Scholar 

  62. Khabbazi S, Goumon Y, Parat MO. Morphine modulates interleukin-4-or breast cancer cell-induced pro-metastatic activation of macrophages. Sci Rep. 2015;5:11389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chang CI, Liao JC, Kuo L. Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Res. 2001;61(3):1100–6.

    CAS  PubMed  Google Scholar 

  64. Chang CI, Liao JC, Kuo L. Arginase modulates nitric oxide production in activated macrophages. Am J Physiol. 1998;274(1 Pt 2):H342–8.

    CAS  PubMed  Google Scholar 

  65. Leo S, Nuydens R, Meert TF. Opioid-induced proliferation of vascular endothelial cells. J Pain Res. 2009;2:59–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, Gupta K. Cox-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer. 2007;97(11):1523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nguyen J, Luk K, Vang D, Soto W, Vincent L, Robiner S, Saavedra R, Li Y, Gupta P, Gupta K. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Singleton PA, Lingen MW, Fekete MJ, Garcia JG, Moss J. Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res. 2006;72(1–2):3–11.

    Article  CAS  PubMed  Google Scholar 

  69. Pasi A, Qu BX, Steiner R, Senn HJ, Bar W, Messiha FS. Angiogenesis: modulation with opioids. Gen Pharmacol. 1991;22(6):1077–9.

    Article  CAS  PubMed  Google Scholar 

  70. Balasubramanian S, Ramakrishnan S, Charboneau R, Wang J, Barke RA, Roy S. Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes. J Mol Cell Cardiol. 2001;33(12):2179–87.

    Article  CAS  PubMed  Google Scholar 

  71. Lam CF, Chang PJ, Huang YS, Sung YH, Huang CC, Lin MW, Liu YC, Tsai YC. Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice. Anesth Analg. 2008;107(2):686–92.

    Article  CAS  PubMed  Google Scholar 

  72. Martin JL, Charboneau R, Barke RA, Roy S. Chronic morphine treatment inhibits lps-induced angiogenesis: implications in wound healing. Cell Immunol. 2010;265(2):139–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Koodie L, Ramakrishnan S, Roy S. Morphine suppresses tumor angiogenesis through a HIF-1alpha/p38MAPK pathway. Am J Pathol. 2010;177(2):984–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. •• Doornebal CW, Vrijland K, Hau CS, Coffelt SB, Ciampricotti M, Jonkers J, de Visser KE, Hollmann MW. Morphine does not facilitate breast cancer progression in two preclinical mouse models for invasive lobular and HER2+ breast cancer. Pain. 2015. doi:https://doi.org/10.1097/j.pain.0000000000000136. This article used a sophisticated mouse model of breast cancer metastasis after tumour resection and showed tumours and angiogenesis were unaffected by analgesic doses of morphine.

  75. Afsharimani B, Doornebal CW, Cabot PJ, Hollmann MW, Parat MO. Comparison and analysis of the animal models used to study the effect of morphine on tumour growth and metastasis. Br J Pharmacol. 2015;172(2):251–9.

    Article  CAS  PubMed  Google Scholar 

  76. Buggy DJ, Borgeat A, Cata J, Doherty DG, Doornebal CW, Forget P, Gottumukkala V, Gottschalk A, Gupta A, Gupta K, Hales TG, et al. Consensus statement from the bja workshop on cancer and anaesthesia. Br J Anaesth. 2015;114(1):2–3.

    Article  CAS  PubMed  Google Scholar 

  77. Zhao M, Zhou G, Zhang Y, Chen T, Sun X, Stuart C, Hanley G, Li J, Zhang J, Yin D. Beta-arrestin2 inhibits opioid-induced breast cancer cell death through Akt and caspase-8 pathways. Neoplasma. 2009;56(2):108–13.

    Article  CAS  PubMed  Google Scholar 

  78. Gonzalez-Nunez V, Noriega-Prieto JA, Rodriguez RE. Morphine modulates cell proliferation through mir133b & mir128 in the neuroblastoma SH-SY5Y cell line. Biochim Biophys Acta. 2014;1842(4):566–72.

    Article  CAS  PubMed  Google Scholar 

  79. Maneckjee R, Minna JD. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. Proc Natl Acad Sci USA. 1990;87(9):3294–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ishikawa M, Tanno K, Kamo A, Takayanagi Y, Sasaki K. Enhancement of tumor growth by morphine and its possible mechanism in mice. Biol Pharm Bull. 1993;16(8):762–6.

    Article  CAS  PubMed  Google Scholar 

  81. Hatzoglou A, Bakogeorgou E, Castanas E. The antiproliferative effect of opioid receptor agonists on the T47D human breast cancer cell line, is partially mediated through opioid receptors. Eur J Pharmacol. 1996;296(2):199–207.

    Article  CAS  PubMed  Google Scholar 

  82. Hatzoglou A, Ouafik L, Bakogeorgou E, Thermos K, Castanas E. Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth. Cancer Res. 1995;55(23):5632–6.

    CAS  PubMed  Google Scholar 

  83. Kampa M, Bakogeorgou E, Hatzoglou A, Damianaki A, Martin PM, Castanas E. Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCap, PC3 and DU145) through a partial interaction with opioid receptors. Eur J Pharmacol. 1997;335(2–3):255–65.

    Article  CAS  PubMed  Google Scholar 

  84. Sueoka E, Sueoka N, Kai Y, Okabe S, Suganuma M, Kanematsu K, Yamamoto T, Fujiki H. Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation. Biochem Biophys Res Commun. 1998;252(3):566–70.

    Article  CAS  PubMed  Google Scholar 

  85. Kawase M, Sakagami H, Furuya K, Kikuchi H, Nishikawa H, Motohashi N, Morimoto Y, Varga A, Molnar J. Cell death-inducing activity of opiates in human oral tumor cell lines. Anticancer Res. 2002;22(1A):211–4.

    CAS  PubMed  Google Scholar 

  86. Zagon IS, McLaughlin PJ. Opioids and the apoptotic pathway in human cancer cells. Neuropeptides. 2003;37(2):79–88.

    Article  CAS  PubMed  Google Scholar 

  87. Yin D, Woodruff M, Zhang Y, Whaley S, Miao J, Ferslew K, Zhao J, Stuart C. Morphine promotes jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3k/Akt/Nf-kappaB pathways. J Neuroimmunol. 2006;174(1–2):101–7.

    Article  CAS  PubMed  Google Scholar 

  88. Mathew B, Lennon FE, Siegler J, Mirzapoiazova T, Mambetsariev N, Sammani S, Gerhold LM, LaRiviere PJ, Chen CT, Garcia JG, Salgia R, et al. The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation. Anesth Analg. 2011;112(3):558–67.

    Article  CAS  PubMed  Google Scholar 

  89. Fujioka N, Nguyen J, Chen C, Li Y, Pasrija T, Niehans G, Johnson KN, Gupta V, Kratzke RA, Gupta K. Morphine-induced epidermal growth factor pathway activation in non-small cell lung cancer. Anesth Analg. 2011;113(6):1353–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhang XL, Chen ML, Zhou SL. Fentanyl inhibits proliferation and invasion of colorectal cancer via beta-catenin. Int J Clin Exp Pathol. 2015;8(1):227–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model. Exp Biol Med. 2011;236(9):1036–50.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Marie-Odile Parat is supported by the Australia and New Zealand College of Anaesthetists. Dr. Bernhard Riedel wishes to thank Drs. Donal Buggy, Vijaya Gottumukkala, and Erica Sloan for their kind assistance in the development of this issue and the reviewing of the articles.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marie-Odile Parat.

Additional information

This article is part of the Topical Collection on Cancer Anesthesia.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xie, N., Parat, MO. Opioid Analgesic Agents and Cancer Cell Biology. Curr Anesthesiol Rep 5, 278–284 (2015). https://doi.org/10.1007/s40140-015-0118-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40140-015-0118-5

Keywords

Navigation