奥曲肽对人肺腺癌A-549细胞系生长抑素受体亚型的表达研究
|
摘要
目的
检测人肺腺癌A-549细胞系中生长抑素受体亚型mRNA和蛋白的表达，探讨奥曲肽作用于人肺腺癌A-549细胞系后生长抑素受体各亚型蛋白和mRNA的表达并分析其表达变化的临床意义以及奥曲肽对细胞株增殖的影响。方法
免疫组化法测定人肺腺癌A-549细胞系中五种生长抑素受体亚型的表达，RT-PCR检测奥曲肽作用前后生长抑素受体亚型mRNA的表达,并进行半定量分析；MTT法检测奥曲肽对细胞株增殖的影响。结果
人肺腺癌A-549细胞系中五中生长抑素受体亚型（SSTR1-5）均有表达，奥曲肽抑制人肺腺癌A-549细胞系的增殖并呈现浓度依赖性；人肺腺癌A-549细胞系表达五种生长抑素受体亚型的mRNA和蛋白，SSTR3和SSTR1的表达量要明显高于SSTR2、SSTR4、SSTR5，P<0.05。奥曲肽作用后SSTR1的mRNA和蛋白表达量明显高于其它四型(P<0.05)，SSTR2、SSTR5mRNA和蛋白的表达量明显高于对照组的SSTR2、SSTR5mRNA和蛋白的表达量(P<0.05)。
结论
1.五种生长抑素受体亚型在人肺腺癌A-549细胞系中均有表达。
2.八肽生长抑素奥曲肽可以明显抑制肺腺癌细胞系的增殖。
3.SSTR1、SSTR2、SSTR5在抑制人肺腺癌A-549细胞系生长和增殖过程中发挥了关键性作用。
Objective To investigate the mRNA and protein expression of somatostatin receptors in human lung cancer A549 cells lines and to explore the mRNA and protein expression of somatostatin receptors with octreotide acting on the human lung cancer A549 cellsand to analyse the clinical significance of the changed expression and the influence of ocetreotide on the proliferation of human lung cancer A549 cells.
Methods RT-PCR and immunocytochemistry were used to detect mRNA and protein expression of somatostatin receptors in human lung cancer A549 cells and to carry out semiquantitative analysis. MTT were used to evaluate the antiproliferative effect of octreotide.
Results The effect of SSTR1-5 on the human lung cancer A549 cells was verified. Octreotide could inhibit the growth of A549 cells in dose dependent manner. The mRNA expression of all 5 subtypes of somatostatin receptors was different. SSTR3 and SSTR1 mRNA expressions were significantly higher than SSTR2,SSTR4,SSTR5 (p<0.05). The mRNA and protein expression of SSTR1 were significantly higher than SSTR2、3、4、5 with octreotide acting on the cells (P<0.05). The mRNA and protein expression of SSTR2 and SSTR5 were significantly higher than control group (P<0.05).
Conclusion 1.All 5 subtypes of somatostatin receptors expression in human lung cancer A549 cells. 2.The proliferation of A549 celle is reduced by octreotide. 3.SSTR1,SSTR2 and SSTR5 play an important role in inhibiting human lung cancer A549 cells growth and proliferation.
检测人肺腺癌A-549细胞系中生长抑素受体亚型mRNA和蛋白的表达，探讨奥曲肽作用于人肺腺癌A-549细胞系后生长抑素受体各亚型蛋白和mRNA的表达并分析其表达变化的临床意义以及奥曲肽对细胞株增殖的影响。方法
免疫组化法测定人肺腺癌A-549细胞系中五种生长抑素受体亚型的表达，RT-PCR检测奥曲肽作用前后生长抑素受体亚型mRNA的表达,并进行半定量分析；MTT法检测奥曲肽对细胞株增殖的影响。结果
人肺腺癌A-549细胞系中五中生长抑素受体亚型（SSTR1-5）均有表达，奥曲肽抑制人肺腺癌A-549细胞系的增殖并呈现浓度依赖性；人肺腺癌A-549细胞系表达五种生长抑素受体亚型的mRNA和蛋白，SSTR3和SSTR1的表达量要明显高于SSTR2、SSTR4、SSTR5，P<0.05。奥曲肽作用后SSTR1的mRNA和蛋白表达量明显高于其它四型(P<0.05)，SSTR2、SSTR5mRNA和蛋白的表达量明显高于对照组的SSTR2、SSTR5mRNA和蛋白的表达量(P<0.05)。
结论
1.五种生长抑素受体亚型在人肺腺癌A-549细胞系中均有表达。
2.八肽生长抑素奥曲肽可以明显抑制肺腺癌细胞系的增殖。
3.SSTR1、SSTR2、SSTR5在抑制人肺腺癌A-549细胞系生长和增殖过程中发挥了关键性作用。
Objective To investigate the mRNA and protein expression of somatostatin receptors in human lung cancer A549 cells lines and to explore the mRNA and protein expression of somatostatin receptors with octreotide acting on the human lung cancer A549 cellsand to analyse the clinical significance of the changed expression and the influence of ocetreotide on the proliferation of human lung cancer A549 cells.
Methods RT-PCR and immunocytochemistry were used to detect mRNA and protein expression of somatostatin receptors in human lung cancer A549 cells and to carry out semiquantitative analysis. MTT were used to evaluate the antiproliferative effect of octreotide.
Results The effect of SSTR1-5 on the human lung cancer A549 cells was verified. Octreotide could inhibit the growth of A549 cells in dose dependent manner. The mRNA expression of all 5 subtypes of somatostatin receptors was different. SSTR3 and SSTR1 mRNA expressions were significantly higher than SSTR2,SSTR4,SSTR5 (p<0.05). The mRNA and protein expression of SSTR1 were significantly higher than SSTR2、3、4、5 with octreotide acting on the cells (P<0.05). The mRNA and protein expression of SSTR2 and SSTR5 were significantly higher than control group (P<0.05).
Conclusion 1.All 5 subtypes of somatostatin receptors expression in human lung cancer A549 cells. 2.The proliferation of A549 celle is reduced by octreotide. 3.SSTR1,SSTR2 and SSTR5 play an important role in inhibiting human lung cancer A549 cells growth and proliferation.
引文
[1]Krantic S. Peptide regulators of the immune system: emphasis on somatostatin.Peptides,2000,21:1941~1964.
[2] Guillermet-Guibert J,Lahlou H,Cordelier P,et al Physiology of somatostatin receptors[J].J Endocrinol Invest,2005,28(11):5.
[3] Dalm VA, van Hagen PM, van Koetsveld PM, et al. Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system. J Clin Endocrinol Metab,2003,88:270-276.
[4] Patel YC. Somatostatin and receptor family. Front Neuroendocrinol,1999,20:157-198.its
[5]刘青光,宋涛,孙昊,等。奥曲肽对人肝癌细胞株MHCC97-H的影响[J]。西安交通大学学报:医学版,2007,28(2):190。
[6]O’Byme KJ, Schally AV, ThomasA, et al Somatostatin,its receptors and analogs, in lung cancer[J]. Chemotherapy,2001,47(Supp12):78.
[7]Casini Raggi C, Calaabro A, Renzi D, et al Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa [J].Clin Cancer Res,2002,8(2):419.
[8]Zalatnai A,Pogany V. Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment, Anticancer Res,2001,21(1A):477-480.
[9]田春桃,韩利艳,范慧娟。奥曲肽对人肺癌细胞株A549的增殖抑制作用。郑州大学学报(医学版),2008,43(1)。
[10]Meyerhof W. The elucidation of somatostatin receptor functions :a current view. Rev Physiol Biochem Pharmaool,1998,133:55-108.
[11]Zapata P D,Ropero P M. Valencia A M, et al. Autocrine, regulation of human prostate carcinoma cell proliferation by somatostatin through themodulation of theSH2 domain containing protein tyrosine phosphatase(SHP)-1, JClin Endocrinol Metab,2002,87(2):915-926.
[12]Ferjoux G, Bousquet C, Cordelier P, et al. Signal transduetion of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris, 2000,94:205-210.
[13]Berruti A, Dogliottil, Mosca A, et al Effcts of the somatostatin analog Lan reotide on the circulating level of chromogranin-A, prostate-specific antigen, and insulin-1ike growth factor-1 in advanced prostate cancer patients[J]. Prostate, 2001,47(3):205.
[14]Gules SA, Drouant GJ, Fuselier J, et al Antitumor and antiangiogenic effects of somatosatinreceptor-targeted in situ readiation with(111) IN-DTPA-JIC 2DL[J]. J Sury Res,2001,97(2):131.
[15]Cascinu S, Del Ferro E, LigiM, et al Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients[J]. CancerInvest,2001,19(1):8.
[16]Mahimainathan L, Ghosh-Choudhury N, Venkatesan BA, et al EGF stimulatesmesangial cell mitogenesis via PB-kinase-mediated MAPK-dependent and AKT kinase-independent manner. Involvement of c-fos and p27 Kip1[J]. Am J Physiol Renal Physiol,2005,289(1):72.
[17]Rostomily RC, Elias M,Deng M, et al Clinical utility of somatostatin receptor scintigraphic imaging in esthesioneuioblastoma: a case study and survey of somatostatin receptor subtype expression[J]. Head Neck,2006,28(4):305.
[18]肖小平,李月琴,徐彬,等。过表达SSTR2通过多种信号途径抑制SSTR2表达阳性的肿瘤生长。中国病理生理杂志,2009,25(7):1254-1261
[19]Lim,Fisher WE,Kim HJ, et al Somatostatin, somatostatin receptors,and pancreatic cancer[J]. World J Surg,2005,29(3):293.
[20]Reubi JC, Zimmermann A, Jonas S, et al. Regulatory peptide receptors in human hepatocellular carcinomas ,Gut,1999,45:766-774.
[21]Blaker M, Schmitz M, Gocht A, et al. Differential expression of somatostatin receptor subtypes in hepatocellular carcinomas. J Hepatol,2004,41:112-118.
[22] Dimitroulopoulos D,Xinopoulos D,Tsamakidis K,et al. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors:randomized placebo-controlled trial[J]. World J Gastroenterol,2007,13 (23):3164-3170
[1] Koutsilieris M,Mitsiades C,Dimopoulos T,et al. Combination of dexameth- asone and a somatostatin analogue in the treatment of advanced prostate cancer. Expert Opin Investig Drug,2002,11(2):283-293.
[2]Li M, Zhang R,Li F,et al. Transfection of SSTR1 and SSTR2 inhibit its Panc-1 cell proliferation and renders Panc-1 cells responsive to somatostatin analogue [J]. J Am Coll Surg,2005,201(4):571-578
[3]Li M, Fisher WE, Kim HJ, et al. Somatostatin, somatostatin receptors, and panc reatic cancer [J]. World J Surg,2005,29(3):293-296
[4] Brown M,Rivier J, Vale W et al Somatostatin analogs with selected biological activities Science,1977;196:1467-1468.
[5] Rens Domiano S, Reisine T. Structural analysis and functional role of the car- bohydrate componnent of somatostatin receptors [J]. J Biol Chem,1991,266(30):20094-20102
[6] Moore SB, van der Hoek J, de Capua A, et al. Discovery of iodinated soma- tostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells [J]. J Med Chem,2005,48(21):6643-6652
[7] Wang CH,Tang CW,Liu CL, et al Inhibitory efffect of octreotide on gastric cancer growth via MAPK pathway [J]. World J Gastroenterol 2003,9(9):1904.
[8] Hatzoglou A, Kampa M, Castanas E Opioid-somatostatin interactions in reg ulating cancer cell growth [J]. FrontBiosci,2005,1(10):244.
[9] Moaeen-ud-Din M, Yang L G. Evolutionary history of the somatostatin and somatostatin receptors [J]. J Genet,2009,88(1):41-53.
[10] Meyerhof W. The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmaool,1998,133:55-108.
[11] Zapata P D,Ropero P M,Valencia A M,et al. Autocrine,regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase SHP-1. J Clin EndocrinolMetab,2002,87(2):915-926.
[12] Szokoloczi O, Schwab R,Petak I, et al. TT232, a novel signal transduction in hibitory compound in the therapy of cancer and inflammatory disease. J Recept Signal Transduct Res,2005,25(4-6):217-235.
[13] Schwab RE, Froidevaux S, Paku S, et al. Antiproliferative efficacy of the so- matostatin analogue TT-232 in human melanoma cells and tumours. Anticancer Res,2001,21(1A):71-75.
[14] Zalatnai A,Pogany V. Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment. Anticancer Res,2001,21(1A):477-480.
[15] Dasgupta P. Somatostatin analogues:multiple roles in cellular proliferation,neoplasia,and angiogenesis. Pharmacol Ther,2004,102(1):61-85.
[16] Garcia de la Torre N, Wass JA, Turner HE. Antiangiogenic effects of somatostatin analogues. Clin Endocrinol(Oxf),2002,57(4):425-441.
[17] Florio T, Morini M, Villa V, et al. Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology, 2003,144(4):1574-1584.
[18] Bates CM, Kegg H, Grady S. Experssion of somatostatin receptors 1 and 2 in the adultmouse kidney [J]. Regul Pept,2004,119(1-2):11.
[19] Masteodimou N,Thermos K The somatostatin receptor(sstl) modulates the release of somatostatin in rat retina [J]. NeurosciLett,2004,356(1):13.
[20] Banzo J, Prats E, Razola P, et al. Scintigraphy atlas of somatostatin receptors in neuroendocrine tumors of the pancreas and carcinoid tumors [J]. Rev Esp Med Nucl,2005,24(4):278-292.
[21] Yan D G,Ou Q J. Somatostatin receptor subtype SSTR2 and SSTR3 mRNA expression in primary hepatic carcinoma [J]. Cancer,2001,20(2):152-155.
[22] Dizeyi N, Konrad L, Bjartell A, et al Localization and Mma expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines [J]. Urol Oncol,2002,7(3):91.
[23] Froidevaux S, Hintermann E, Torok M, et al Differential regulation of somatostatin receptor type2 expression in AR4-2J tumor cells implanted into mice during octreotide treatment [J]. Cancer Res,1999,59(15):3652.
[24] Nikolopoulon A,Maina T, Sotiriou P, et al Tetraamine-modified octretide and octretate: labeling with mTC and preclinical comparison in AR4-2J tumor-bearing mice [J]. J Pept Sci,2006,12(2):124.
[25] Vaccarili M, Lococo A, Fabiani F,et al. Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer. Tumori,2000,86(3):224-228.
[26] Tejeda M, Gaal D, Barna K,et al. The antitumor activity of the somatostatin structural derivative(TT-232) on different human tumor xenografts. Anticancer Res,2003,23(5A):4061-4066.
[27] Kiaris H, Schally AV, Nagy A,et al. A targeted cytotoxic somatostatin analogue, AN-238, inhibits the growth of H-69 small cell lungcarcinoma and H-157 non-SCLC in nude mice. Eur J Cancer,2001,(5):620-628.
[28] Szereday Z,Schally AV, Szeppeshazi K, et al. Effective treatment of H838 human non-small cell carcinoma with a targeted cytotoxic somatostatin analogy AN-238. Int J Oncol,2003,22(5):1141-1146.
[29] Patel Yc. Somatostatin and its receptor family. Front Neuroen docrinol, 1999, 20: 157-198
[30] Buckmaster PS, Otero-Corchon V, Rubinstein M, et al.Heightened seizure severity in somatostatin knockoutmice. Epilepsy Res,2002,48:43-56
[31] Nilsson CL, Brinkmalm A, Minthon L, et al. Processing of neuropeptide Y, galanin and somatostatin in the cerebrospinal fluid of patients with Alzheimer’s disease and frontotemporal dementia. Peptides,2001,22:2105-2112.
[32] Kang TC, Park SK,Do SG, et al. The over expression of somatostatin in gerbil entorhinal cortex induced by seizure. Brain Res,2000,882:55-61.
[33] Guillermet-Guibert J, Lahlou H. Cordelier P, et al Physiology of somatostatin receptors [J]. J Endocrinol Invest,2005,28(11):5
[34] Capelb A, Krenning E,Bemard B, et al 111In-labelled somatostatin analogues in a rat tumor model: somatostatin receptor status and effects of peptide receptor radionuclide therapy [J]. Eur J Nucl Med Mol Imaging,2005,32(11):1288.
[35] Kwekkeboom DJ, Mueller-Brand J, Paganelli G, et al Overview of results of peptide receptor radionuclide therapy with radiolabeled somatostatin analogs [J]. J NuclMed,2005,46(supp11):62.
[36] Letsch M,Schally AV, Szepeshazi K,et al Effective treatment of experimental androogen sensitive and androgen independent intraosseous prostate cancer with targeted cytotoxic somatostatin analogue AN-238 [J]. J Urol,2004,171(2):911.
[2] Guillermet-Guibert J,Lahlou H,Cordelier P,et al Physiology of somatostatin receptors[J].J Endocrinol Invest,2005,28(11):5.
[3] Dalm VA, van Hagen PM, van Koetsveld PM, et al. Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system. J Clin Endocrinol Metab,2003,88:270-276.
[4] Patel YC. Somatostatin and receptor family. Front Neuroendocrinol,1999,20:157-198.its
[5]刘青光,宋涛,孙昊,等。奥曲肽对人肝癌细胞株MHCC97-H的影响[J]。西安交通大学学报:医学版,2007,28(2):190。
[6]O’Byme KJ, Schally AV, ThomasA, et al Somatostatin,its receptors and analogs, in lung cancer[J]. Chemotherapy,2001,47(Supp12):78.
[7]Casini Raggi C, Calaabro A, Renzi D, et al Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa [J].Clin Cancer Res,2002,8(2):419.
[8]Zalatnai A,Pogany V. Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment, Anticancer Res,2001,21(1A):477-480.
[9]田春桃,韩利艳,范慧娟。奥曲肽对人肺癌细胞株A549的增殖抑制作用。郑州大学学报(医学版),2008,43(1)。
[10]Meyerhof W. The elucidation of somatostatin receptor functions :a current view. Rev Physiol Biochem Pharmaool,1998,133:55-108.
[11]Zapata P D,Ropero P M. Valencia A M, et al. Autocrine, regulation of human prostate carcinoma cell proliferation by somatostatin through themodulation of theSH2 domain containing protein tyrosine phosphatase(SHP)-1, JClin Endocrinol Metab,2002,87(2):915-926.
[12]Ferjoux G, Bousquet C, Cordelier P, et al. Signal transduetion of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris, 2000,94:205-210.
[13]Berruti A, Dogliottil, Mosca A, et al Effcts of the somatostatin analog Lan reotide on the circulating level of chromogranin-A, prostate-specific antigen, and insulin-1ike growth factor-1 in advanced prostate cancer patients[J]. Prostate, 2001,47(3):205.
[14]Gules SA, Drouant GJ, Fuselier J, et al Antitumor and antiangiogenic effects of somatosatinreceptor-targeted in situ readiation with(111) IN-DTPA-JIC 2DL[J]. J Sury Res,2001,97(2):131.
[15]Cascinu S, Del Ferro E, LigiM, et al Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients[J]. CancerInvest,2001,19(1):8.
[16]Mahimainathan L, Ghosh-Choudhury N, Venkatesan BA, et al EGF stimulatesmesangial cell mitogenesis via PB-kinase-mediated MAPK-dependent and AKT kinase-independent manner. Involvement of c-fos and p27 Kip1[J]. Am J Physiol Renal Physiol,2005,289(1):72.
[17]Rostomily RC, Elias M,Deng M, et al Clinical utility of somatostatin receptor scintigraphic imaging in esthesioneuioblastoma: a case study and survey of somatostatin receptor subtype expression[J]. Head Neck,2006,28(4):305.
[18]肖小平,李月琴,徐彬,等。过表达SSTR2通过多种信号途径抑制SSTR2表达阳性的肿瘤生长。中国病理生理杂志,2009,25(7):1254-1261
[19]Lim,Fisher WE,Kim HJ, et al Somatostatin, somatostatin receptors,and pancreatic cancer[J]. World J Surg,2005,29(3):293.
[20]Reubi JC, Zimmermann A, Jonas S, et al. Regulatory peptide receptors in human hepatocellular carcinomas ,Gut,1999,45:766-774.
[21]Blaker M, Schmitz M, Gocht A, et al. Differential expression of somatostatin receptor subtypes in hepatocellular carcinomas. J Hepatol,2004,41:112-118.
[22] Dimitroulopoulos D,Xinopoulos D,Tsamakidis K,et al. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors:randomized placebo-controlled trial[J]. World J Gastroenterol,2007,13 (23):3164-3170
[1] Koutsilieris M,Mitsiades C,Dimopoulos T,et al. Combination of dexameth- asone and a somatostatin analogue in the treatment of advanced prostate cancer. Expert Opin Investig Drug,2002,11(2):283-293.
[2]Li M, Zhang R,Li F,et al. Transfection of SSTR1 and SSTR2 inhibit its Panc-1 cell proliferation and renders Panc-1 cells responsive to somatostatin analogue [J]. J Am Coll Surg,2005,201(4):571-578
[3]Li M, Fisher WE, Kim HJ, et al. Somatostatin, somatostatin receptors, and panc reatic cancer [J]. World J Surg,2005,29(3):293-296
[4] Brown M,Rivier J, Vale W et al Somatostatin analogs with selected biological activities Science,1977;196:1467-1468.
[5] Rens Domiano S, Reisine T. Structural analysis and functional role of the car- bohydrate componnent of somatostatin receptors [J]. J Biol Chem,1991,266(30):20094-20102
[6] Moore SB, van der Hoek J, de Capua A, et al. Discovery of iodinated soma- tostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells [J]. J Med Chem,2005,48(21):6643-6652
[7] Wang CH,Tang CW,Liu CL, et al Inhibitory efffect of octreotide on gastric cancer growth via MAPK pathway [J]. World J Gastroenterol 2003,9(9):1904.
[8] Hatzoglou A, Kampa M, Castanas E Opioid-somatostatin interactions in reg ulating cancer cell growth [J]. FrontBiosci,2005,1(10):244.
[9] Moaeen-ud-Din M, Yang L G. Evolutionary history of the somatostatin and somatostatin receptors [J]. J Genet,2009,88(1):41-53.
[10] Meyerhof W. The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmaool,1998,133:55-108.
[11] Zapata P D,Ropero P M,Valencia A M,et al. Autocrine,regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase SHP-1. J Clin EndocrinolMetab,2002,87(2):915-926.
[12] Szokoloczi O, Schwab R,Petak I, et al. TT232, a novel signal transduction in hibitory compound in the therapy of cancer and inflammatory disease. J Recept Signal Transduct Res,2005,25(4-6):217-235.
[13] Schwab RE, Froidevaux S, Paku S, et al. Antiproliferative efficacy of the so- matostatin analogue TT-232 in human melanoma cells and tumours. Anticancer Res,2001,21(1A):71-75.
[14] Zalatnai A,Pogany V. Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment. Anticancer Res,2001,21(1A):477-480.
[15] Dasgupta P. Somatostatin analogues:multiple roles in cellular proliferation,neoplasia,and angiogenesis. Pharmacol Ther,2004,102(1):61-85.
[16] Garcia de la Torre N, Wass JA, Turner HE. Antiangiogenic effects of somatostatin analogues. Clin Endocrinol(Oxf),2002,57(4):425-441.
[17] Florio T, Morini M, Villa V, et al. Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology, 2003,144(4):1574-1584.
[18] Bates CM, Kegg H, Grady S. Experssion of somatostatin receptors 1 and 2 in the adultmouse kidney [J]. Regul Pept,2004,119(1-2):11.
[19] Masteodimou N,Thermos K The somatostatin receptor(sstl) modulates the release of somatostatin in rat retina [J]. NeurosciLett,2004,356(1):13.
[20] Banzo J, Prats E, Razola P, et al. Scintigraphy atlas of somatostatin receptors in neuroendocrine tumors of the pancreas and carcinoid tumors [J]. Rev Esp Med Nucl,2005,24(4):278-292.
[21] Yan D G,Ou Q J. Somatostatin receptor subtype SSTR2 and SSTR3 mRNA expression in primary hepatic carcinoma [J]. Cancer,2001,20(2):152-155.
[22] Dizeyi N, Konrad L, Bjartell A, et al Localization and Mma expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines [J]. Urol Oncol,2002,7(3):91.
[23] Froidevaux S, Hintermann E, Torok M, et al Differential regulation of somatostatin receptor type2 expression in AR4-2J tumor cells implanted into mice during octreotide treatment [J]. Cancer Res,1999,59(15):3652.
[24] Nikolopoulon A,Maina T, Sotiriou P, et al Tetraamine-modified octretide and octretate: labeling with mTC and preclinical comparison in AR4-2J tumor-bearing mice [J]. J Pept Sci,2006,12(2):124.
[25] Vaccarili M, Lococo A, Fabiani F,et al. Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer. Tumori,2000,86(3):224-228.
[26] Tejeda M, Gaal D, Barna K,et al. The antitumor activity of the somatostatin structural derivative(TT-232) on different human tumor xenografts. Anticancer Res,2003,23(5A):4061-4066.
[27] Kiaris H, Schally AV, Nagy A,et al. A targeted cytotoxic somatostatin analogue, AN-238, inhibits the growth of H-69 small cell lungcarcinoma and H-157 non-SCLC in nude mice. Eur J Cancer,2001,(5):620-628.
[28] Szereday Z,Schally AV, Szeppeshazi K, et al. Effective treatment of H838 human non-small cell carcinoma with a targeted cytotoxic somatostatin analogy AN-238. Int J Oncol,2003,22(5):1141-1146.
[29] Patel Yc. Somatostatin and its receptor family. Front Neuroen docrinol, 1999, 20: 157-198
[30] Buckmaster PS, Otero-Corchon V, Rubinstein M, et al.Heightened seizure severity in somatostatin knockoutmice. Epilepsy Res,2002,48:43-56
[31] Nilsson CL, Brinkmalm A, Minthon L, et al. Processing of neuropeptide Y, galanin and somatostatin in the cerebrospinal fluid of patients with Alzheimer’s disease and frontotemporal dementia. Peptides,2001,22:2105-2112.
[32] Kang TC, Park SK,Do SG, et al. The over expression of somatostatin in gerbil entorhinal cortex induced by seizure. Brain Res,2000,882:55-61.
[33] Guillermet-Guibert J, Lahlou H. Cordelier P, et al Physiology of somatostatin receptors [J]. J Endocrinol Invest,2005,28(11):5
[34] Capelb A, Krenning E,Bemard B, et al 111In-labelled somatostatin analogues in a rat tumor model: somatostatin receptor status and effects of peptide receptor radionuclide therapy [J]. Eur J Nucl Med Mol Imaging,2005,32(11):1288.
[35] Kwekkeboom DJ, Mueller-Brand J, Paganelli G, et al Overview of results of peptide receptor radionuclide therapy with radiolabeled somatostatin analogs [J]. J NuclMed,2005,46(supp11):62.
[36] Letsch M,Schally AV, Szepeshazi K,et al Effective treatment of experimental androogen sensitive and androgen independent intraosseous prostate cancer with targeted cytotoxic somatostatin analogue AN-238 [J]. J Urol,2004,171(2):911.