G蛋白偶联受体与肿瘤发生发展相关性研究现状
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摘要
目的:研究G蛋白偶联受体(GPCRs)在人类肿瘤细胞中的表达,以及与人类恶性肿瘤发生发展的关系。方法:检索中国知识资源总库CNKI系列数据库、西文生物医学期刊数据库和PubMed数据库检索系统,分别以"G蛋白偶联受体(GPCRs)"和"肿瘤"、"生长抑素受体(SSTRs)"和"肿瘤"、"G蛋白偶联受体30(GPR30/GPER)"和"肿瘤"、"β肾上腺素受体(β-AR)"和"肿瘤"、"腺苷受体(AR)"和"肿瘤"、"胃泌素受体(CCK-BR)"和"肿瘤"为关键词,检索2000-01-2012-10国内外GPCRs与肿瘤方面的文献,CNKI中检索到21 207篇文献,西文生物医学期刊数据库中检索到8 317篇文献,PubMed中检索到5 674篇文献。纳入标准:1)GPCRs的信号传导通路;2)GPCRs与肿瘤的关系;3)GPCRs与肿瘤的靶向治疗。根据标准,纳入34篇文献进行分析。结果:GPCRs参与了胃癌、大肠癌、肺癌和乳腺癌等多种肿瘤的发生和发展过程,在肿瘤生长中起重要作用。GPCRs与人类肿瘤的增殖、侵袭和转移等多种恶性生物学行为密切相关,涉及到多种信号传导通路。GPCRs激动剂或者抑制剂与受体结合后,通过细胞内相应的信号传导通路能够影响肿瘤的生长,为临床肿瘤靶向分子治疗提供了提供实验理论依据。结论:GPCRs的研究能为人类肿瘤的诊治提供新的依据,也有利于发展新的抗癌药物作用靶点。
OBJECTIVE : To explore G protein-coupled receptors expression in human tumour cell and its correlation with development of human carcinoma.METHODS :" GPRs " and " tumour "," SSTRs " and " tumour "," GPR30 / GPER " and " tumour "," β-AR " and " tumour "," AR " and " tumour "," CCK-BR " and " tumour " as key words were respectively searched by PubMed 、 CNKI and EMCC serises full-text database retrieval system from 2000-01to 2012-10.There were 21 207papers in CNKI,8 317in EMCC and 5 674in PubMed.The selection standards : 1) The signal pathway of GPCRs;2) The relationship of GPCRs and tumour;3) GPCRs targeted therapy.According to the selection standrads 34papers were analyzed finally.RESULTS : GPCRs participated in development of many kinds of tumors,such as Gastric cancer,Colorectal cancer,Lung cancer and breast cancer.GPCRs play an important role in tumor growth and associate with tumorigenesis,invasiveness and angiogenesis,and involve a variety of signaling pathways.Agonist or Inhibitor of GPCRs combined with receptors can affect tumor growth through intracellular corresponding signaling pathways,which provide theory basis for tumor targeted molecular therapy.CONCLUSION : GPCRs provide a new prognostic marker as well as a strategy of targeted therapy.
OBJECTIVE : To explore G protein-coupled receptors expression in human tumour cell and its correlation with development of human carcinoma.METHODS :" GPRs " and " tumour "," SSTRs " and " tumour "," GPR30 / GPER " and " tumour "," β-AR " and " tumour "," AR " and " tumour "," CCK-BR " and " tumour " as key words were respectively searched by PubMed 、 CNKI and EMCC serises full-text database retrieval system from 2000-01to 2012-10.There were 21 207papers in CNKI,8 317in EMCC and 5 674in PubMed.The selection standards : 1) The signal pathway of GPCRs;2) The relationship of GPCRs and tumour;3) GPCRs targeted therapy.According to the selection standrads 34papers were analyzed finally.RESULTS : GPCRs participated in development of many kinds of tumors,such as Gastric cancer,Colorectal cancer,Lung cancer and breast cancer.GPCRs play an important role in tumor growth and associate with tumorigenesis,invasiveness and angiogenesis,and involve a variety of signaling pathways.Agonist or Inhibitor of GPCRs combined with receptors can affect tumor growth through intracellular corresponding signaling pathways,which provide theory basis for tumor targeted molecular therapy.CONCLUSION : GPCRs provide a new prognostic marker as well as a strategy of targeted therapy.
引文
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[8]李飞,罗浩军,罗平,等.雌激素受体GPR30、ERα和PR在甲状腺癌组织中的表达及相关性[J].第三军医大学学报,2011,33(16):1691-1694.
[9]Filardo EJ,Quinn JA,Bland KI,et al.Estrogen-induced activa-tion of Erk-1and Erk-2requires the G protein-coupled receptorhomolog,GPR30,and occurs via trans-activation of the epidermalgrowth factor receptor through release of HB-EGF[J].Mol En-docrinol,2000,14(10):1649-1660.
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[12]Ruan SQ,Wang ZH,Wang SW,et al.Heregulin-b1-induced GPR30upregulation Promotes the migration and invasion potential of SkBr3breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway[J].Bio-chem Biophys Res Commun,2012,420(2):385-390.
[13]Smith HO,Arias-Pulido H,Kuo DY,et al.GPR30predicts poorsurvival for ovarian cancer[J].Gynecol Oncol,2009,114(3):465-471.
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[15]吴婷婷,龙方懿,贾朝莉,等.G蛋白偶联受体在雌激素诱导人甲状腺未分化癌FRO细胞增殖中的作用及其机制[J].第三军医大学学报,2011,33(2):164-168.
[16]Chimento A,Sirianni R,Delalande C,et al.17beta-Estradiol acti-vates rapid signaling pathways involved in rat pachytene sper-matocytes apoptosis through GPR30and ERalpha[J].Mol CellEndocrinol,2010,320(1-2):136-144.
[17]Balhuizen A,Kumar R,Amisten S,et al.Activation of G protein-coupled receptor 30 modulates hormone secretion and counter-acts cytokine-induced apoptosis in pancreatic islets of female mice[J].Mol Cell Endocrinol,2010,320(1-2):16-24.
[18]McGraw DW,Liggett SB.Molecular mechanisms of beta2-ad-renergic receptor function and regulation[J].Proc Am ThoracSoc,2005,2(4):292-296.
[19]Perrone MG,Notarnicola M,Caruso MG,et al.Upregulation ofbeta3-adrenergic receptor mRNA in human colon cancer:apre-liminary study[J].Oncology,2008,75(3-4):224-229.
[20]Weddle DL,Tithoff P,Williams M,et al.Beta-adrenergic growthregulation of human cancer cell lines derived from pancreatic duc-tal carcinomas[J].Carcinogenesis,2001,22(3):473-479.
[21]Askari MD,Tsao MS,Schuller HM.The tobaeco-specific carcin-ogen,4-(methyinitrosamino)-1-(3-pyridyl)-1-butanone stimu-lates proliferation of immortalized human pancreatic duct epithe-lia through beta-adrenergic transactivation of EGF receptors[J].J Cancer Res Clin Oncol,2005,131(10):639-648.
[22]Schuller HM.Mechanisms of smoking-related lung and pancre-atic adenocarcinoma development[J].Nat Rev Cancer,2002,2(6):455-463.
[23]Schuller HM,Cekanova M.NNK-induced hamster lung adeno-carcinomas over-express beta2-adrenergic and EGFR signalingpathways[J].Lung Cancer,2005,49(1):35-45.
[24]郭坤,马清涌,胡恒通,等.β受体在人胰腺癌细胞株中的表达及其在细胞侵袭中的作用[J].中华实验外科杂志,2009,26(7):827-829.
[25]李静,尹林林,张钢峰,等.大肠癌组织A3AR蛋白表达及A3ARmRNA基因扩增临床意义的探讨[J].中华肿瘤防治杂志,2011,18(4):275-283.
[26]Merighi S,Benini A,Mirandola P,et al.Adenosine modulates vascu-lar endothelial growth factor expression via hypoxia-inducible factor-1in human glioblastoma cells[J].Biochem Pharmacol,2006,72(1):19-31.
[27]Merighi S,Benini A,Mirandola P,et al.Caffeine inhibits adeno-sine-induced accumulation of hypoxia-inducible factor-1alpha,vascular endothelial growth factor,and interleukin-8expressionin hypoxic human colon cancer cells[J].Mol Pharmacol,2007,72(2):395-406.
[28]Bar-Yehuda S,Madi L,Silberman D,et al.CF101,an agonist tothe A3adenosine receptor,enhances the chemotherapeutic effectof 5-fluorouracil in a colon carcinoma murine model[J].Neopla-sia,2005,7(1):85-90.
[29]Merighi S,Benini A,Mirandola P,et al.A3adenosine receptor acti-vation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase1/2phosphorylation in A375human melanoma cells[J].J BiolChem,2005,280(20):19516-19526.
[30]Scott N,Millward E,Cartwright EJ,et al.Gastrin releasing pep-tide and gastrin releasing peptide receptor expression in gastroin-testinal carcinoid tumours[J].J Clin Pathol,2004,57(2):189-192.
[31]明媚,于皆平,周燕红,等.p38MAPK在胃泌素诱导结肠癌细胞表达u-PA中的作用[J],中华肿瘤杂志,2007,29(1):4-8.
[32]曹俊,邹晓平,诸葛宇征,等.胃泌素对人结肠癌细胞Colo320WT中β-catenin/Tcf-4通路的影响[J].中国药理学通报,2008,24(4):441-443.
[33]曹俊,于皆平,周岚,等.胃泌素对结肠癌细胞中粘着斑激酶通路下游E-钙粘蛋白/β-连环蛋白复合物的影响[J].中华消化杂志,2006,26(12):813-817.
[34]赵迎春,茆家定,吴佩,等.胃泌素对大肠癌SW480细胞STAT3信号通路影响的研究[J].中华肿瘤防治杂志,2009,16(20):1538-1540.
[2]Chen JS,Liang QM,Li HS,et al.Octreotide inhibits growth ofcolonic cancer SW480cells by modulating the Wnt/β-cateninpathway[J].Pharmazie,2009,64(2):126-131.
[3]Tsagarakis NJ,Drygiannakis I,Batistakis AG,et al.Octreotideinduces caspase activation and apoptosis in human hepatomaHepG2cells[J].World J Gastroenterol,2011,17(3):313-321.
[4]Strosberg J,Kvols L.Antiproliferative effect of somatostatin an-alogs in gastroenteropancreatic neuroendocrine tumors[J].World J Gastroenterol,2010,16(24):2963-2970.
[5]Florio T.Molecular mechanisms of the antiproliferative activityof somatostatin receptors(SSTRs)in neuroendocrine tumors[J].Front Biosci,2008,13:822-840.
[6]Watt HL,Kharmate GD,Kumar U.Somatostatin receptors 1and 5heterodimerize with epidermal growth factor receptor:agonist-de-pendent modulation of the downstream MAPK signalling pathway inbreast cancer cells[J].Cell Signal,2009,21(3):428-439.
[7]Bousquet C,Puente E,Buscail L,et al.Antiproliferative effect ofsomatostatin and analogs[J].Chemotherapy,2001,47(Suppl2):30-39.
[8]李飞,罗浩军,罗平,等.雌激素受体GPR30、ERα和PR在甲状腺癌组织中的表达及相关性[J].第三军医大学学报,2011,33(16):1691-1694.
[9]Filardo EJ,Quinn JA,Bland KI,et al.Estrogen-induced activa-tion of Erk-1and Erk-2requires the G protein-coupled receptorhomolog,GPR30,and occurs via trans-activation of the epidermalgrowth factor receptor through release of HB-EGF[J].Mol En-docrinol,2000,14(10):1649-1660.
[10]郭瑞霞,郭会敏,苑中甫,等.G蛋白偶联受体30和磷酸化AKT在子宫内膜腺癌中表达及意义[J].现代妇产科进展,2009,18(12):881-884.
[11]Smith HO,Arias-Pulido H,Kuo DY,et al.GPR30predicts poorsurvival for ovarian cancer[J].Gynecol Oncol,2009,114(3):465-471.
[12]Ruan SQ,Wang ZH,Wang SW,et al.Heregulin-b1-induced GPR30upregulation Promotes the migration and invasion potential of SkBr3breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway[J].Bio-chem Biophys Res Commun,2012,420(2):385-390.
[13]Smith HO,Arias-Pulido H,Kuo DY,et al.GPR30predicts poorsurvival for ovarian cancer[J].Gynecol Oncol,2009,114(3):465-471.
[14]Albanito L,Madeo A,Lappano R,et al.G protein-coupled recep-tor30(GPR30)mediates gene expression changes and growth re-sponse to 17beat-estradiol and selective GPR30ligand G-1in o-varian cancer cells[J].Cancer Res,2007,67(4):1859-1866.
[15]吴婷婷,龙方懿,贾朝莉,等.G蛋白偶联受体在雌激素诱导人甲状腺未分化癌FRO细胞增殖中的作用及其机制[J].第三军医大学学报,2011,33(2):164-168.
[16]Chimento A,Sirianni R,Delalande C,et al.17beta-Estradiol acti-vates rapid signaling pathways involved in rat pachytene sper-matocytes apoptosis through GPR30and ERalpha[J].Mol CellEndocrinol,2010,320(1-2):136-144.
[17]Balhuizen A,Kumar R,Amisten S,et al.Activation of G protein-coupled receptor 30 modulates hormone secretion and counter-acts cytokine-induced apoptosis in pancreatic islets of female mice[J].Mol Cell Endocrinol,2010,320(1-2):16-24.
[18]McGraw DW,Liggett SB.Molecular mechanisms of beta2-ad-renergic receptor function and regulation[J].Proc Am ThoracSoc,2005,2(4):292-296.
[19]Perrone MG,Notarnicola M,Caruso MG,et al.Upregulation ofbeta3-adrenergic receptor mRNA in human colon cancer:apre-liminary study[J].Oncology,2008,75(3-4):224-229.
[20]Weddle DL,Tithoff P,Williams M,et al.Beta-adrenergic growthregulation of human cancer cell lines derived from pancreatic duc-tal carcinomas[J].Carcinogenesis,2001,22(3):473-479.
[21]Askari MD,Tsao MS,Schuller HM.The tobaeco-specific carcin-ogen,4-(methyinitrosamino)-1-(3-pyridyl)-1-butanone stimu-lates proliferation of immortalized human pancreatic duct epithe-lia through beta-adrenergic transactivation of EGF receptors[J].J Cancer Res Clin Oncol,2005,131(10):639-648.
[22]Schuller HM.Mechanisms of smoking-related lung and pancre-atic adenocarcinoma development[J].Nat Rev Cancer,2002,2(6):455-463.
[23]Schuller HM,Cekanova M.NNK-induced hamster lung adeno-carcinomas over-express beta2-adrenergic and EGFR signalingpathways[J].Lung Cancer,2005,49(1):35-45.
[24]郭坤,马清涌,胡恒通,等.β受体在人胰腺癌细胞株中的表达及其在细胞侵袭中的作用[J].中华实验外科杂志,2009,26(7):827-829.
[25]李静,尹林林,张钢峰,等.大肠癌组织A3AR蛋白表达及A3ARmRNA基因扩增临床意义的探讨[J].中华肿瘤防治杂志,2011,18(4):275-283.
[26]Merighi S,Benini A,Mirandola P,et al.Adenosine modulates vascu-lar endothelial growth factor expression via hypoxia-inducible factor-1in human glioblastoma cells[J].Biochem Pharmacol,2006,72(1):19-31.
[27]Merighi S,Benini A,Mirandola P,et al.Caffeine inhibits adeno-sine-induced accumulation of hypoxia-inducible factor-1alpha,vascular endothelial growth factor,and interleukin-8expressionin hypoxic human colon cancer cells[J].Mol Pharmacol,2007,72(2):395-406.
[28]Bar-Yehuda S,Madi L,Silberman D,et al.CF101,an agonist tothe A3adenosine receptor,enhances the chemotherapeutic effectof 5-fluorouracil in a colon carcinoma murine model[J].Neopla-sia,2005,7(1):85-90.
[29]Merighi S,Benini A,Mirandola P,et al.A3adenosine receptor acti-vation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase1/2phosphorylation in A375human melanoma cells[J].J BiolChem,2005,280(20):19516-19526.
[30]Scott N,Millward E,Cartwright EJ,et al.Gastrin releasing pep-tide and gastrin releasing peptide receptor expression in gastroin-testinal carcinoid tumours[J].J Clin Pathol,2004,57(2):189-192.
[31]明媚,于皆平,周燕红,等.p38MAPK在胃泌素诱导结肠癌细胞表达u-PA中的作用[J],中华肿瘤杂志,2007,29(1):4-8.
[32]曹俊,邹晓平,诸葛宇征,等.胃泌素对人结肠癌细胞Colo320WT中β-catenin/Tcf-4通路的影响[J].中国药理学通报,2008,24(4):441-443.
[33]曹俊,于皆平,周岚,等.胃泌素对结肠癌细胞中粘着斑激酶通路下游E-钙粘蛋白/β-连环蛋白复合物的影响[J].中华消化杂志,2006,26(12):813-817.
[34]赵迎春,茆家定,吴佩,等.胃泌素对大肠癌SW480细胞STAT3信号通路影响的研究[J].中华肿瘤防治杂志,2009,16(20):1538-1540.