阿片生长因子甲硫氨酸脑啡肽抗肿瘤作用研究进展
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摘要
甲硫氨酸脑啡肽是一种内源性阿片生长因子,它除了具有阿片肽类镇痛、免疫调控等共性以外,还对细胞的增生和更新、肿瘤生长、伤口愈合、血管发生等具有比较强的抑制作用。甲硫氨酸脑啡肽可以作用于细胞的生长周期,从而达到抑制肿瘤细胞生长的作用。本文对甲硫氨酸脑啡肽的药理作用、抗肿瘤作用及其作用机制的研究现状进行综述。
Methionine enkephalin(Met-ENK) is a kind of endogenous opioid growth factor.In addition to the role of analgesia and immunoregulation,Met-ENK also has strong inhibitory effects on cell proliferation and renewing,tumor growth,wound healing and angiogenesis.It can inhibit growth of neoplastic cells through the inhibition of cell cycles.In this article,advances in research on the pharmacological actions,antineoplastic effect and its mechanism of Met-ENK were summarized.
Methionine enkephalin(Met-ENK) is a kind of endogenous opioid growth factor.In addition to the role of analgesia and immunoregulation,Met-ENK also has strong inhibitory effects on cell proliferation and renewing,tumor growth,wound healing and angiogenesis.It can inhibit growth of neoplastic cells through the inhibition of cell cycles.In this article,advances in research on the pharmacological actions,antineoplastic effect and its mechanism of Met-ENK were summarized.
引文
[1]Zagon I S,Hytrek S D,Smith J P,et al.Opioid growth fac-tor(OGF)inhibits human pancreatic cancer transplanted intonude mice[J].Cancer Lett,1997,112(2):167-175.
[2]Zagon I S,Smith J P,McLaughlin P J.Human pancreaticcancer cell proliferation in tissue culture is tonically inhibitedby opioid growth factor[J].Int J Oncol,1999,14(3):577-584.
[3]Smith J P,Conter R L,Bingaman S I,et al.Treatment ofadvanced pancreatic cancer with opioid growth factor:phaseⅠ[J].Anticancer Drugs,2004,15(3):203-209.
[4]张领兵.甲硫氨酸脑啡肽研究进展及其应用前景[J].国外医学免疫学分册,2005,28(6):354-356.Zhang LingBing.Advances in research on methionine enkeph-alin and its application perspectives[J].Foreign Med Sci SecImmunol,2005,28(6):354-356.In Chinese.
[5]Zagon I S,Verderame M F,McLaughlin P J.The biology ofthe opioid growth factor receptor(OGFr)[J].Brain Res Rev,2002,38(3):351-376.
[6]Piva M,Moreno J I,Jenkins F S,et al.In vitro modulationof cytokine expression by enkephalin-derived peptides[J].Neuroimmunomodulation,2005,12(6):339-347.
[7]Zagon I S,Ruth T B,McLaughlin P J.Nucleocytoplasmicdistribution of opioid growth factor and its receptor in tongueepithelium[J].Anat Rec A Discov Mol Cell Evol Biol,2005,282(1):24-37.
[8]徐颖,田玉科,田学愎,等.可诱导表达脑啡肽的大鼠星形胶质细胞株的构建[J].第四军医大学学报,2006,27(5):400-403.Xu Ying,Tian YuKe,Tian XueBi,et al.Construction of animmortalized rat astrocyte strain with inducible enkephalinexpression[J].J Fourth Mil Med Univ,2006,27(5):400-403.In Chinese with English abstract.
[9]Liu X H,Huang D A,Yang F Y,et al.A new cytokine:thepossible effect pathway of methionine enkephalin[J].World JGastroenterol,2003,9(1):169-173.
[10]Zagon I S,Rahn K A,Bonneau R H,et al.Opioid growthfactor suppresses expression of experimental autoimmune en-cephalomyelitis[J].Brain Res,2010,1310:154-161.
[11]Zagon I S,Donahue R N,Bonneau R H,et al.B lymphocyteproliferation is suppressed by the opioid growth factor-opioidgrowth factor receptor axis:implication for the treatment ofautoimmune diseases[J].Immunobiology,2011,216(1-2):173-183.
[12]Rahn K A,McLaughlin P J,Zagon I S.Prevention anddiminished expression of experimental autoimmune encepha-lomyelitis by low dose naltrexone(LDN)or opioid growthfactor(OGF)for an extended period:therapeutic implica-tions for multiple sclerosis[J].Brain Res,2011,1381:243-253.
[13]Malendowicz L K,Rebuffat P,Tortorella C,et al.Effects ofmet-enkephalin on cell proliferation in different models ofadrenocortical-cell growth[J].Int J Mol Med,2005,15(5):841-845.
[14]Li P F,Hao Y S,Zhang F X,et al.Signaling pathwayinvolved in methionine enkephalin-promoted survival oflymphocytes infected by simian immunodeficiency virus in theearly stage in vitro[J].Int Immunopharmacol,2004,4(1):79-90.
[15]药立波.医学分子生物学[M].3版.北京:人民卫生出版社,2008:8,107.Yao LiBo.Medical molecular biology[M].3rd ed.Beijing:People’s Health Press,2008:8,107.In Chinese.
[16]Fanning J,Hossler C A,Kesterson J P,et al.Expression ofthe opioid growth factor-opioid growth factor receptor axis inhuman ovarian cancer[J].Gynecol Oncol,2012,124(2):319-324.
[17]Donahue R N,McLaughlin P J,Zagon I S.The opioid growthfactor(OGF)and low dose naltrexone(LDN)suppresshuman ovarian cancer progression in mice[J].Gynecol Oncol,2011,122(2):382-388.
[18]Donahue R N,McLaughlin P J,Zagon I S.Cell proliferationof human ovarian cancer is regulated by the opioid growthfactor-opioid growth factor receptor axis[J].Am J PhysiolRegul Integr Comp Physiol,2009,296(6):R1716-R1725.
[19]Cheng Fan,McLaughlin P J,Verderame M F,et al.TheOGF-OGFr axis utilizes the p16INK4aand p21 WAF1/CIP1 path-ways to restrict normal cell proliferation[J].Mol Biol Cell,2009,20(1):319-327.
[20]Zagon I S,Verderame M F,Hankins J,et al.Overexpressionof the opioid growth factor receptor potentiates growth inhibi-tion in human pancreatic cancer cells[J].Int J Oncol,2007,30(4):775-783.
[21]McLaughlin P J,Lerin R J,Zagon I S.Opioid growth factor(OGF)inhibits the progression of human squamous cell carci-noma of the head and neck transplanted into nude mice[J].Cancer Lett,2003,199(2):209-217.
[22]McLaughlin P J,Zagon I S,Park S S,et al.Growth inhibitionof thyroid follicular cell-derived cancers by the opioid growthfactor(OGF)-opioid growth factor receptor(OGFr)axis[J].BMC Cancer,2009,9:369.
[23]邢恩鸿,胡建功,王宁,等.阿片生长因子抑制乳腺癌细胞生长的研究[J].天津医药,2011,39(1):10-13.Xing EnHong,Hu JianGong,Wang Ning,et al.Inhibitoryeffect of opioid growth factor on human breast carcinoma cells[J].Tianjin Med J,2011,39(1):10-13.In Chinese withEnglish abstract.
[24]Singh A,Jayanthan A,Farran A,et al.Induction of apoptosisin pediatric acute lymphoblastic leukemia(ALL)cells by thetherapeutic opioid methadone and effective synergy with Bcl-2inhibition[J].Leuk Res,2011,35(12):1649-1657.
[25]Hao YanSheng,Zhang FengXue,Huang DongAi,et al.Possi-ble effect pathway of methionine enkephalin on apoptosis ofCEM x174cells induced by simian immunodeficiency virus inearly stages of infection[J].Chin J Biochem Mol Biol,2003:19(3):305-311.郝艳生,张奉学,黄冬爱,等.甲硫氨酸脑啡肽对猴免疫缺陷病毒早期感染引起CEM x174细胞凋亡的可能作用[J].中国生物化学与分子生物学报,2003:19(3):305-311.In Englishwith Chinese abstract.
[26]Kramer H K,Simon E J.Role of protein kinase C(PKC)inagonist-induced mu-opionid receptor down-regulation:Ⅱ.Activation and involvement of alpha,epsilon,and zeta iso-forms of PKC[J].J Neurochem,1999,72(2):594-604.
[27]黄冬爱,杨非易,李平风,等.甲硫氨酸脑啡肽和抗δ阿片受体抗体对小鼠骨髓瘤细胞信号传递系统的作用[J].中国生物化学与分子生物学报,2000,16(5):660-664.Huang DongAi,Yang FeiYi,Li PingFeng,et al.The role ofmethionine-enkephalin and antibody against opioid receptoron signal transduction system in mouse NS-1cells[J].Chin JBiochem Mol Biol,2000,16(5):660-664.In Chinese withEnglish abstract.
[2]Zagon I S,Smith J P,McLaughlin P J.Human pancreaticcancer cell proliferation in tissue culture is tonically inhibitedby opioid growth factor[J].Int J Oncol,1999,14(3):577-584.
[3]Smith J P,Conter R L,Bingaman S I,et al.Treatment ofadvanced pancreatic cancer with opioid growth factor:phaseⅠ[J].Anticancer Drugs,2004,15(3):203-209.
[4]张领兵.甲硫氨酸脑啡肽研究进展及其应用前景[J].国外医学免疫学分册,2005,28(6):354-356.Zhang LingBing.Advances in research on methionine enkeph-alin and its application perspectives[J].Foreign Med Sci SecImmunol,2005,28(6):354-356.In Chinese.
[5]Zagon I S,Verderame M F,McLaughlin P J.The biology ofthe opioid growth factor receptor(OGFr)[J].Brain Res Rev,2002,38(3):351-376.
[6]Piva M,Moreno J I,Jenkins F S,et al.In vitro modulationof cytokine expression by enkephalin-derived peptides[J].Neuroimmunomodulation,2005,12(6):339-347.
[7]Zagon I S,Ruth T B,McLaughlin P J.Nucleocytoplasmicdistribution of opioid growth factor and its receptor in tongueepithelium[J].Anat Rec A Discov Mol Cell Evol Biol,2005,282(1):24-37.
[8]徐颖,田玉科,田学愎,等.可诱导表达脑啡肽的大鼠星形胶质细胞株的构建[J].第四军医大学学报,2006,27(5):400-403.Xu Ying,Tian YuKe,Tian XueBi,et al.Construction of animmortalized rat astrocyte strain with inducible enkephalinexpression[J].J Fourth Mil Med Univ,2006,27(5):400-403.In Chinese with English abstract.
[9]Liu X H,Huang D A,Yang F Y,et al.A new cytokine:thepossible effect pathway of methionine enkephalin[J].World JGastroenterol,2003,9(1):169-173.
[10]Zagon I S,Rahn K A,Bonneau R H,et al.Opioid growthfactor suppresses expression of experimental autoimmune en-cephalomyelitis[J].Brain Res,2010,1310:154-161.
[11]Zagon I S,Donahue R N,Bonneau R H,et al.B lymphocyteproliferation is suppressed by the opioid growth factor-opioidgrowth factor receptor axis:implication for the treatment ofautoimmune diseases[J].Immunobiology,2011,216(1-2):173-183.
[12]Rahn K A,McLaughlin P J,Zagon I S.Prevention anddiminished expression of experimental autoimmune encepha-lomyelitis by low dose naltrexone(LDN)or opioid growthfactor(OGF)for an extended period:therapeutic implica-tions for multiple sclerosis[J].Brain Res,2011,1381:243-253.
[13]Malendowicz L K,Rebuffat P,Tortorella C,et al.Effects ofmet-enkephalin on cell proliferation in different models ofadrenocortical-cell growth[J].Int J Mol Med,2005,15(5):841-845.
[14]Li P F,Hao Y S,Zhang F X,et al.Signaling pathwayinvolved in methionine enkephalin-promoted survival oflymphocytes infected by simian immunodeficiency virus in theearly stage in vitro[J].Int Immunopharmacol,2004,4(1):79-90.
[15]药立波.医学分子生物学[M].3版.北京:人民卫生出版社,2008:8,107.Yao LiBo.Medical molecular biology[M].3rd ed.Beijing:People’s Health Press,2008:8,107.In Chinese.
[16]Fanning J,Hossler C A,Kesterson J P,et al.Expression ofthe opioid growth factor-opioid growth factor receptor axis inhuman ovarian cancer[J].Gynecol Oncol,2012,124(2):319-324.
[17]Donahue R N,McLaughlin P J,Zagon I S.The opioid growthfactor(OGF)and low dose naltrexone(LDN)suppresshuman ovarian cancer progression in mice[J].Gynecol Oncol,2011,122(2):382-388.
[18]Donahue R N,McLaughlin P J,Zagon I S.Cell proliferationof human ovarian cancer is regulated by the opioid growthfactor-opioid growth factor receptor axis[J].Am J PhysiolRegul Integr Comp Physiol,2009,296(6):R1716-R1725.
[19]Cheng Fan,McLaughlin P J,Verderame M F,et al.TheOGF-OGFr axis utilizes the p16INK4aand p21 WAF1/CIP1 path-ways to restrict normal cell proliferation[J].Mol Biol Cell,2009,20(1):319-327.
[20]Zagon I S,Verderame M F,Hankins J,et al.Overexpressionof the opioid growth factor receptor potentiates growth inhibi-tion in human pancreatic cancer cells[J].Int J Oncol,2007,30(4):775-783.
[21]McLaughlin P J,Lerin R J,Zagon I S.Opioid growth factor(OGF)inhibits the progression of human squamous cell carci-noma of the head and neck transplanted into nude mice[J].Cancer Lett,2003,199(2):209-217.
[22]McLaughlin P J,Zagon I S,Park S S,et al.Growth inhibitionof thyroid follicular cell-derived cancers by the opioid growthfactor(OGF)-opioid growth factor receptor(OGFr)axis[J].BMC Cancer,2009,9:369.
[23]邢恩鸿,胡建功,王宁,等.阿片生长因子抑制乳腺癌细胞生长的研究[J].天津医药,2011,39(1):10-13.Xing EnHong,Hu JianGong,Wang Ning,et al.Inhibitoryeffect of opioid growth factor on human breast carcinoma cells[J].Tianjin Med J,2011,39(1):10-13.In Chinese withEnglish abstract.
[24]Singh A,Jayanthan A,Farran A,et al.Induction of apoptosisin pediatric acute lymphoblastic leukemia(ALL)cells by thetherapeutic opioid methadone and effective synergy with Bcl-2inhibition[J].Leuk Res,2011,35(12):1649-1657.
[25]Hao YanSheng,Zhang FengXue,Huang DongAi,et al.Possi-ble effect pathway of methionine enkephalin on apoptosis ofCEM x174cells induced by simian immunodeficiency virus inearly stages of infection[J].Chin J Biochem Mol Biol,2003:19(3):305-311.郝艳生,张奉学,黄冬爱,等.甲硫氨酸脑啡肽对猴免疫缺陷病毒早期感染引起CEM x174细胞凋亡的可能作用[J].中国生物化学与分子生物学报,2003:19(3):305-311.In Englishwith Chinese abstract.
[26]Kramer H K,Simon E J.Role of protein kinase C(PKC)inagonist-induced mu-opionid receptor down-regulation:Ⅱ.Activation and involvement of alpha,epsilon,and zeta iso-forms of PKC[J].J Neurochem,1999,72(2):594-604.
[27]黄冬爱,杨非易,李平风,等.甲硫氨酸脑啡肽和抗δ阿片受体抗体对小鼠骨髓瘤细胞信号传递系统的作用[J].中国生物化学与分子生物学报,2000,16(5):660-664.Huang DongAi,Yang FeiYi,Li PingFeng,et al.The role ofmethionine-enkephalin and antibody against opioid receptoron signal transduction system in mouse NS-1cells[J].Chin JBiochem Mol Biol,2000,16(5):660-664.In Chinese withEnglish abstract.