The role of morphine in regulation of cancer cell growth

Naunyn-Schmiedeberg's Archives of Pharmacology

Volumn 384, Issue 3, 2011, Pages 221-230

  Gach, Katarzyna ^a   Wyrębska, Anna ^a   Fichna, Jakub ^a   Janecka, Anna ^a  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

Author keywords

Angiogenesis; Apoptosis; Metastasis; Migration; Proliferation

Indexed keywords

BIM PROTEIN; CASPASE 3; CASPASE 9; CELECOXIB; COLLAGEN TYPE 4; CYCLOOXYGENASE 2; CYTOCHROME C; DOXORUBICIN; GELATINASE A; GELATINASE B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 4; INTERLEUKIN 6; MESSENGER RNA; MORPHINE; MU OPIATE RECEPTOR; NALOXONE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3 KINASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PLASMINOGEN ACTIVATOR INHIBITOR 2; PROSTAGLANDIN E2; PROTEIN BCL 2; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; SIGMA 2 OPIATE RECEPTOR; STRESS ACTIVATED PROTEIN KINASE; UROKINASE; UROKINASE RECEPTOR;

APOPTOSIS; BREAST CANCER; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTINUOUS INFUSION; DRUG ANTAGONISM; DRUG BLOOD LEVEL; DRUG MEGADOSE; DRUG POTENTIATION; ENZYME ACTIVATION; GLIOBLASTOMA; HUMAN; LEWIS CARCINOMA; LOW DRUG DOSE; LYMPHOCYTE; MACROPHAGE; METASTASIS; MITOGENESIS; MONOCYTE; NATURAL KILLER CELL; NEUROBLASTOMA; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; TUMOR VASCULARIZATION; UPREGULATION;

EID: 80054920188     PISSN: 00281298     EISSN: 14321912     Source Type: Journal    
DOI: 10.1007/s00210-011-0672-4     Document Type: Review

References (103)

1. ArerangaiahR, ChalasaniN,Udager AM, Weber ML, Manivel JC, Griffin RJ, Song CW, Gupta K (2007) Opioids induce renal abnormalities in tumor-bearing mice. Nephron Exp Nephrol 105:e80-e89 (Pubitemid 46438567)
2. Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255-260 (Pubitemid 29164042)
3. Balasubramanian S, Ramakrishnan S, Charboneau R, Wang J, Barke RA, Roy S (2001) Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes. J Mol Cell Cardiol 33:2179-2187 (Pubitemid 34073059)
4. Birnbaum Y, Ye Y, Rosanio S, Tavackoli S, Hu ZY, Schwarz ER, Uretsky BF (2005) Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury. Cardiovasc Res 65:345-355 (Pubitemid 40082476)
5. Bonnet MP, Beloeil H, Benhamou D, Mazoit JX, Asehnoune K (2008) The mu opioid receptor mediates morphine-induced tumor necrosis factor and interleukin-6 inhibition in toll-like receptor 2-stimulated monocytes. Anesth Analg 106:1142-1149 (Pubitemid 351450539)
6. Börner C, Stumm R, Hollt V, Kraus J (2007) Comparative analysis of mu-opioid receptor expression in immune and neuronal cells. J Neuroimmunol 188:56-63 (Pubitemid 47095015)
7. Börner C, Warnick B, Smida M, Hartig R, Lindquist JA, Schraven B, Höllt V, Kraus J (2009) Mechanisms of opioid-mediated inhibition of human T cell receptor signaling. J Immunol 183:882-889
8. Brekken RA, Thorpe PE (2001) Vascular endothelial growth factor and vascular targeting of solid tumors. Anticancer Res 21:4221-4229 (Pubitemid 34240953)
9. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249-257
10. Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T (2004) Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci USA 101:591-596 (Pubitemid 38084681)
11. Chen C, Farooqui M, Gupta K (2006) Morphine stimulates vascular endothelial growth factor-like signaling in mouse retinal endothelial cells. Curr Neurovasc Res 3:171-180 (Pubitemid 44198470)
12. Chen YL, Law PY, Loh HH (2008) The other side of the opioid story: modulation of cell growth and survival signaling. Curr Med Chem 15:772-778 (Pubitemid 351516793)
13. Cheng WF, Chen LK, Chen CA, Chang MC, Hsiao PN, Su YN, Lee CN, Jeng HJ, Hsieh CY, Sun WZ (2006) Chimeric DNAvaccine reverses morphine-induced immunosuppression and tumorigenesis. Mol Ther 13:203-210
14. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647-656 (Pubitemid 37328916)
15. Cory S, Huang DC, Adams JM (2003) The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22:8590-8607 (Pubitemid 38028528)
16. Crawford KW, Bowen WD (2002) Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines. Cancer Res 62:313-322 (Pubitemid 34074021)
17. Crawford KW, Coop A, Bowen WD (2002) Sigma(2) receptors regulate changes in sphingolipid levels in breast tumor cells. Eur J Pharmacol 443:207-209 (Pubitemid 34603617)
18. Diao CT, Li L, Lau SY, Wong TM, Wong NS (2000) Kappa-opioid receptor potentiates apoptosis via a phospholipase C pathway in the CNE2 human epithelial tumor cell line. Biochim Biophys Acta 1499:49-62
19. Duffy MJ, Duggan C (2004) The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer. Clin Biochem 37:541-548 (Pubitemid 38845017)
20. Eisenstein TK, Hilburger ME (1998) Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol 83:36-44 (Pubitemid 28280949)
21. Engbring JA, Kleinman HK (2003) The basement membrane matrix in malignancy. J Pathol 200:465-470 (Pubitemid 36818246)
22. Farooqui M, Geng ZH, Stephenson EJ, Zaveri N, Yee D, Gupta K (2006) Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther 5:611-620
23. Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, Gupta K (2007) COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer 97:1523-1531 (Pubitemid 350175846)
24. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581-611 (Pubitemid 39099316)
25. Fichna J, Janecka A (2004) Opioid peptides in cancer. Cancer Metastasis Rev 23:351-366 (Pubitemid 38881818)
26. Folkman J, D'Amore PA (1996) Blood vessel formation: what is its molecular basis? Cell 87:1153-1155 (Pubitemid 27010098)
27. Fulda S, Debatin KM (2006) Modulation of apoptosis signaling for cancer therapy. Arch Immunol Ther Exp (Warsz) 54:173-175 (Pubitemid 44257337)
28. Gach K, Szemraj J, Fichna J, Piestrzeniewicz M, Delbro DS, Janecka A (2009) The influence of opioids on urokinase plasminogen activator on protein and mRNA level in MCF-7 breast cancer cell line. Chem Biol Drug Des 74:390-396
29. Gach K, Szemraj J, Wyrebska A, Janecka A (2011) The influence of opioids on matrix metalloproteinase-2 and-9 secretion and mRNA levels in MCF-7 breast cancer cell line. Mol Biol Rep 38:1231-1236
30. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309-1312 (Pubitemid 28406816)
31. Griffin RJ, Williams BW, Wild R, Cherrington JM, Park H, Song CW (2002) Simultaneous inhibition of the receptor kinase activity of vascular endothelial, fibroblast, and platelet-derived growth factors suppresses tumor growth and enhances tumor radiation response. Cancer Res 62:1702-1706 (Pubitemid 34408492)
32. Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, Hebbel RP (2002) Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res 62:4491-4498 (Pubitemid 34827313)
33. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70 (Pubitemid 30046295)
34. Harimaya Y, Koizumi K, Andoh T, Nojima H, Kuraishi Y, Saiki I (2002) Potential ability of morphine to inhibit the adhesion, invasion and metastasis of metastatic colon 26-L5 carcinoma cells. Cancer Lett 187:121-127 (Pubitemid 35279340)
35. Harrison LM, Kastin AJ, Zadina JE (1998) Opiate tolerance and dependence: receptors, G-proteins, and antiopiates. Peptides 19:1603-1630 (Pubitemid 29015903)
36. Hatsukari I, Hitosugi N, Matsumoto I, Nagasaka H, Sakagami H (2003) Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines. Anticancer Res 23:2413-2417 (Pubitemid 36897110)
37. Hatsukari I, Hitosugi N, Ohno R, Hashimoto K, Nakamura S, Satoh K, Nagasaka H, Matsumoto I, Sakagami H (2007) Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res 27:857-864 (Pubitemid 46586991)
38. Hatzoglou A, Bakogeorgou E, Castanas E (1996) The antiproliferative effect of opioid receptor agonists on the T47D human breast cancer cell line, is partially mediated through opioid receptors. Eur J Pharmacol 296:199-207 (Pubitemid 26041520)
39. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770-776
40. Hsiao PN, Chang MC, Cheng WF, Chen CA, Lin HW, Hsieh CY, Sun WZ (2009) Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways. Toxicology 256:83-91
41. Iglesias M, Segura MF, Comella JX, Olmos G (2003) Mu-opioid receptor activation prevents apoptosis following serum withdrawal in differentiated SH-SY5Y cells and cortical neurons via phosphatidylinositol 3-kinase. Neuropharmacology 44(4):482-492 (Pubitemid 36293980)
42. Ishikawa M, Tanno K, Kamo A, Takayanagi Y, Sasaki K (1993) Enhancement of tumor growth by morphine and its possible mechanism in mice. Biol Pharm Bull 16:762-766 (Pubitemid 23288165)
43. Janecka A, Fichna J, Kosson P, Zalewska-Kaszubska J, Krajewska U, Mirowski M, Rozalski M (2004) Binding of the new morphi-ceptin analogs to human MCF-7 breast cancer cells and their effect on growth. Regul Pept 120:237-241 (Pubitemid 38726212)
44. Jespersen C, Doller A, Akool e, Bachmann M, Muller R, Gutwein P, Muhl H, Pfeilschifter J, Eberhardt W (2009) Molecular mechanisms of nitric oxide-dependent inhibition of TPA-induced matrix metalloproteinase-9 (MMP-9) in MCF-7 cells. J Cell Physiol 219:276-287
45. Kapasi AA, Coscia SA, Pandya MP, Singhal PC (2004) Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte apoptosis by disparate ways. J Neuroimmunol 148:86-96 (Pubitemid 38229561)
46. Kaufmann SH, Hengartner MO (2001) Programmed cell death: alive and well in the new millennium. Trends Cell Biol 11:526-534 (Pubitemid 33079147)
47. Kawase M, Sakagami H, Furuya K, Kikuchi H, Nishikawa H, Motohashi N, Morimoto Y, Varga A, Molnar J (2002) Cell death-inducing activity of opiates in human oral tumor cell lines. Anticancer Res 22:211-214 (Pubitemid 34475300)
48. Kieffer BL (1999) Opioids: first lessons from knockout mice. Trends Pharmacol Sci 20:19-26 (Pubitemid 29304521)
49. Kieffer BL, Gaveriaux-Ruff C (2002) Exploring the opioid system by gene knockout. Prog Neurobiol 66:285-306 (Pubitemid 34518287)
50. King T, Vardanyan A, Majuta L, Melemedjian O, Nagle R, Cress AE, Vanderah TW, Lai J, Porreca F (2007) Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain 132:154-168 (Pubitemid 47494569)
51. Koodie L, Ramakrishnan S, Roy S (2010) Morphine suppresses tumor angiogenesis through a HIF-1alpha/p38MAPK pathway. Am J Pathol 177:984-997
52. Kraus J (2009) Regulation of mu-opioid receptors by cytokines. Front Biosci 1:164-170, Schol. Ed
53. Lam CF, Chang PJ, Huang YS, Sung YH, Huang CC, Lin MW, Liu YC, Tsai YC (2008) Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice. Anesth Analg 107:686-692
54. Lazarczyk M, Matyja E, Lipkowski AW (2010) A comparative study of morphine stimulation and biphalin inhibition of human glioblastoma T98G cell proliferation in vitro. Peptides 31:1606-1612
55. Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL (2002) Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 62:625-631 (Pubitemid 34126930)
56. Lin X, Li Q, Wang YJ, Ju YW, Chi ZQ, Wang MW, Liu JG (2007) Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcrip-tional activation in neuroblastoma SH-SY5Y cells. Biochem J 406:215-221 (Pubitemid 47310952)
57. Lin X, Wang YJ, Li Q, Hou YY, Hong MH, Cao YL, Chi ZQ, Liu JG (2009) Chronic high-dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway. FEBS J 276:2022-2036
58. Lynch CC, Matrisian LM (2002) Matrix metalloproteinases in tumor-host cell communication. Differentiation 70:561-573 (Pubitemid 36194320)
59. MacFarlane AS, Peng X, Meissler JJ Jr, Rogers TJ, Geller EB, Adler MW, Eisenstein TK (2000) Morphine increases susceptibility to oral Salmonella typhimurium infection. J Infect Dis 181:1350-1358
60. Maneckjee R, Biswas R, Vonderhaar BK (1990) Binding of opioids to human MCF-7 breast cancer cells and their effects on growth. Cancer Res 50:2234-2238 (Pubitemid 20134474)
61. Mantyh PW (2006) Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci 7:797-809 (Pubitemid 44435262)
62. Mao J, Sung B, Ji RR, Lim G (2002) Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neuro-toxic mechanism. J Neurosci 22:7650-7661 (Pubitemid 35386364)
63. Mathew B, Lennon F, Siegler J, Gerhold L, Mambetsariev N, Moreno-Vinasco L, Garcia J, Salgia R, Moss J, Singleton P (2009) The mu-opioid receptor regulates Lewis lung carcinoma tumor growth and metastasis. Mol Cancer Ther 8:C78
64. Mignatti P, Rifkin DB (2000) Nonenzymatic interactions between proteinases and the cell surface: novel roles in normal and malignant cell physiology. Adv Cancer Res 78:103-157
65. Moon TD (1988) The effect of opiates upon prostatic carcinoma cell growth. Biochem Biophys Res Commun 153:722-727
66. Moss J, Rosow CE (2008) Development of peripheral opioid antagonists' new insights into opioid effects. Mayo Clin Proc 83:1116-1130
67. Nedelec E, Abid A, Cipolletta C, Presle N, Terlain B, Netter P, Jouzeau J (2001) Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat chondrocyte: lack of contribution to loss of cartilage anabolism. Biochem Pharmacol 61:965-978 (Pubitemid 32247385)
68. Nylund G, Pettersson A, Bengtsson C, Khorram-Manesh A, Nordgren S, Delbro DS (2008) Functional expression of mu-opioid receptors in the human colon cancer cell line, HT-29, and their localization in human colon. Dig Dis Sci 53:461-466 (Pubitemid 351170037)
69. Odunayo A, Dodam JR, Kerl ME, DeClue AE (2010) Immunomodula-tory effects of opioids. J Vet Emerg Crit Care 20:376-385 (San. Antonio.)
70. Page GG, Ben-Eliyahu S, Yirmiya R, Liebeskind JC (1993) Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain 54:21-28 (Pubitemid 23200567)
71. Pasi A, Qu BX, Steiner R, Senn HJ, Bar W, Messiha FS (1991) Angiogenesis: modulation with opioids. Gen Pharmacol 22:1077-1079
72. Pasternak GW (1993) Pharmacological mechanisms of opioid analgesics. Clin Neuropharmacol 16:1-18 (Pubitemid 23028493)
73. Peterson PK, Molitor TW, Chao CC (1993) Mechanisms of morphine-induced immunomodulation. Biochem Pharmacol 46:343-348 (Pubitemid 23239982)
74. Rasmussen M, Zhu W, Tonnesen J, Cadet P, Tonnesen E, Stefano GB (2002) Effects of morphine on tumour growth. Neuro Endocrinol Lett 23:193-198 (Pubitemid 34741926)
75. Reisine T, Bell GI (1993) Molecular biology of opioid receptors. Trends Neurosci 16:506-510 (Pubitemid 23341958)
76. Risdahl JM, Khanna KV, Peterson PK, Molitor TW (1998) Opiates and infection. J Neuroimmunol 83:4-18 (Pubitemid 28280946)
77. Roy S, Wang J, Charboneau R, Loh HH, Barke RA (2005) Morphine induces CD4+ Tcell IL-4 expression through an adenylyl cyclase mechanism independent of the protein kinase A pathway. J Immunol 175:6361-6367 (Pubitemid 41598876)
78. Sacerdote P, Manfredi B, Mantegazza P, Panerai AE (1997) Anti-nociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol 121:834-840 (Pubitemid 27260792)
79. Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P (1993) Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci USA 90:7240-7244 (Pubitemid 23222425)
80. Salvemini D, Seibert K, Masferrer JL, Misko TP, Currie MG, Needleman P (1994) Endogenous nitric oxide enhances prostaglandin production in a model of renal inflammation. J Clin Invest 93:1940-1947 (Pubitemid 24143071)
81. Sartorius U, Schmitz I, Krammer PH (2001) Molecular mechanisms of death-receptor-mediated apoptosis. Chembiochem 2:20-29
82. Sasamura T, Nakamura S, Iida Y, Fujii H, Murata J, Saiki I, Nojima H, Kuraishi Y (2002) Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol 441:185-191 (Pubitemid 34626170)
83. Schmitz R (1985) Friedrich Wilhelm Serturner and the discovery of morphine. Pharm Hist 27:61-74
84. Shapiro RL, Duquette JG, Roses DF, Nunes I, Harris MN, Kamino H, Wilson EL, Rifkin DB (1996) Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. Cancer Res 56:3597-3604 (Pubitemid 26251658)
85. Shariftabrizi A, Nifli AP, Ansari M, Saadat F, Ebrahimkhani MR, Alizadeh N, Nasseh A, Alexaki VI, Dehpour AR, Castanas E, Khorramizadeh MR (2006) Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine. Eur J Pharmacol 530:33-39 (Pubitemid 43037121)
86. Simon RH, Arbo TE (1986) Morphine increases metastatic tumor growth. Brain Res Bull 16:363-367 (Pubitemid 16071493)
87. Singleton PA, Moss J (2010) Effect of perioperative opioids on cancer recurrence: a hypothesis. Future Oncol 6:1237-1242
88. Smith MT, Wright AW, Williams BE, Stuart G, Cramond T (1999) Cerebrospinal fluid and plasma concentrations of morphine, morphine-3- glucuronide, and morphine-6-glucuronide in patients before and after initiation of intracerebroventricular morphine for cancer pain management. Anesth Analg 88:109-116 (Pubitemid 29025157)
89. Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS (1995) Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation. J Biol Chem 270:30290-30293
90. Sueoka N, Sueoka E, Okabe S, Fujiki H (1996) Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mRNA expression. Carcinogenesis 17:2337-2341 (Pubitemid 26402230)
91. Sueoka E, Sueoka N, Kai Y, Okabe S, Suganuma M, Kanematsu K, Yamamoto T, Fujiki H (1998) Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation. Biochem Biophys Res Commun 252:566-570 (Pubitemid 28556817)
92. Suzuki S, Chuang LF, Doi RH, Chuang RY (2003) Morphine suppresses lymphocyte apoptosis by blocking p53-mediated death signaling. Biochem Biophys Res Commun 308:802-808 (Pubitemid 36976532)
93. Tegeder I, Geisslinger G (2004) Opioids as modulators of cell death and survival-unraveling mechanisms and revealing new indications. Pharmacol Rev 56:351-369 (Pubitemid 39096595)
94. Tegeder I, Grosch S, Schmidtko A, Haussler A, Schmidt H, Niederberger E, Scholich K, Geisslinger G (2003) G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells: involvement of p53 phosphorylation. Cancer Res 63:1846-1852 (Pubitemid 36460847)
95. Ustun F, Durmus-Altun G, Altaner S, Tuncbilek N, Uzal C, Berkarda S (2010) Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC. Med. Oncol (in press)
96. Wang CZ, Li XL, Sun S, Xie JT, Aung HH, Tong R, McEntee E, Yuan CS (2009) Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells. Anticancer Res 29:2927-2932
97. Widel MS, Widel M (2006) Mechanisms of metastasis and molecular markers of malignant tumor progression. I. Colorectal cancer. Postepy Hig Med Dosw (Online) 60:453-470
98. Wu WR, Zheng JW, Li N, Bai HQ, Zhang KR, Li Y (1999) Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in dihydroetorphine-dependent mice. Eur J Pharmacol 366:261-269 (Pubitemid 29080791)
99. Yeager MP, Colacchio TA (1991) Effect of morphine on growth of metastatic colon cancer in vivo. Arch Surg 126:454-456
100. Yeager MP, Colacchio TA, Yu CT, Hildebrandt L, Howell AL, Weiss J, Guyre PM (1995) Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity in volunteers. Anesthesiology 83:500-508
101. Zadina JE, Kastin AJ, Ge LJ, Hackler L (1994) Mu, delta, and kappa opiate receptor binding of Tyr-MIF-1 and of Tyr-W-MIF-1, its active fragments, and two potent analogs. Life Sci 55:L461-L466
102. Zagon IS, Hytrek SD, Lang CM, Smith JP, McGarrity TJ, Wu Y, McLaughlin PJ (1996) Opioid growth factor ([Met5]enkephalin) prevents the incidence and retards the growth of human colon cancer. Am J Physiol 271:R780-R786
103. Zong J, Pollack GM (2000) Morphine antinociception is enhanced in mdr1a gene-deficient mice. Pharm Res 17:749-753 (Pubitemid 30670642)