蛇毒解离素抗肿瘤研究进展

摘要/Abstract

摘要： 细胞膜表面受体在疾病中的作用越来越受到关注, 整合素就是其中之一, 它在机体内通过在细胞与细胞之间、细胞与细胞外基质之间发挥黏附作用从而影响多种疾病的发生。蛇毒具有多种抗肿瘤活性成分, 其中解离素的研究近年来较为深入。解离素特异性地针对整合素的黏附作用, 在抗血栓、抗肿瘤等方面发挥作用, 本文就蛇毒解离素的种类、抗肿瘤活性及机制、临床应用等作一综述。

关键词: 蛇毒, 整合素, 解离素

Abstract: The function of cellular membrane receptor has been paid more attention inmany dieases.Integrin is one of them.The major function of integrin is maintaining the proper structure of tissues by organization of cellcell and cell-extracelluar matrix tethering.The initiation and prolongation of many diseases are promoted by these receptors.Disintegrin is one important component of the snake venom.It inhibit the adhesive attraction of integrin particularly.This review summarizes the types and the biological activities of snake venom disintegrins, as well as discusses there potential clinical application of the study, such as anti-tumor, anticoagulation, and various human diseases.

Key words: snake venom, integrin, disintegrin

中图分类号:

R730.5

张晔, 芮景. 蛇毒解离素抗肿瘤研究进展[J]. 中国临床药理学与治疗学, 2007, 12(9): 984-988.

ZHANG Ye, RUI Jing. Research progress of snake venom disintegrin in treatment of tumor[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 984-988.

参考文献

1 张正明, 芮景.蛇毒抗肿瘤作用研究进展 [J].国际肿瘤学杂志, 2006;33:354-357.
2 Hood JD, Cheresh DA.Role of integrins in cell invasion and migration [J].Nat Rev Cancer, 2002;2:91-100.
3 Stupack DG, Cheresh DA.Get a ligand, get a life :integrins, signaling and cell survival [J].Cell Sci, 2002;115:3729-3738.
4 McLane MA, Kuehar MA, Brando C, et al.New insights on disintegrin-receptor interactions:eristostatin and melanoma cels [J].Haemostasis, 2001;31:177-182.
5 Sanz L, Chen RQ, Perez A, et al.cDNA cloning and functional expression of jerdostatin, a novel RTS-disintegrin from Trimeresurus jerdonii and a specific antagonist of the alpha1beta1 integrin [J].Biol Chem, 2005;280 :40714-40722.
6 Gaslc GJ, Gasic TB, Guermazi S, et al.Platelet-tumor-cel1 interaction in mice :The role of platelets in the spread of malignant disease [J].Cancer, 1973;l1:704-718.
7 Prevost N, Kato H, Bodin L, et al.Platelet integrin adhesive functions and signaling [J].Methods Enzymol, 2007;426 :103-115.
8 Ma YQ, Qin J, Plow EF.Platelet integrin alpha(IIb) beta(3) : activation mechanisms [J].Thromb Haemost, 2007;5:1345-1352.
9 Okuda D, Morita T.Purification and characterization of a new RGD KGD-containing dimeric disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus:the unique effect of piscivostatin on platelet aggregation [J].Biochem, 2001; 130:407-415.
10 Chuang WJ, Wu CH, Huang HN, et al.Comparison of the binding character of triflavin on resting and activated alphaIIbbeta3 integrin in human platelets by electron microscopy [J]. Thromb Res, 2003;109:37-46.
11 Amirkhosravi A, Mousa SA, Amay aM, et al.Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb IIIa antagonist XV454 [J].Thromb Haemost, 2003; 90 :549-554.
12 Beviglia L, Stewart GJ, Niewiarowski S.Effect of four disintegrins on the adhesive and metastatic properties of B16F10 melanoma cells in a murine model [J].Oncol Res, 1995;7:7-20.
13 Marques JA, George JK, Smith IJ, et al.A barbourin-albumin fusion protein that is slowly cleared in vivo retains the ability to inhibit platelet aggregation in vitro [J].Thromb Haemost, 2001;86:902-908.
14 Swaim MW, Chiang HS, Huang TF.Characterisation of platelet aggregation induced by PC-3 human prostate adenocarcinoma cells and inhibited by venom peptides, trigramin and rhodostomin [J].Cancer, 1996;32:715-721.
15 Shimokawa K, Jia LG, Shannon JD, et al.Isolation, sequence analysis, and biological activity of atrolysin E D, the non-RGD disintegrin domain from Crotalus atrox venom [J].Arch Biochem Biophys, 1998;354 :239-246.
16 Chung KH, Kim SH, Han KY, et al.Inhibitory effect of salmosin, a Korean snake venom-derived disintegrin, on the integrin alphav-mediated proliferation of SK-Mel-2 human melanoma cells [J].Pharm Pharmacol, 2003;55 :1577-1582.
17 Sheu JR, Lin CH, Chung JL, et al.Triflavin, an Arg-gly-Asp containing peptide, inhibits the adhesion of tumor cells to matrix proteins via binding to multiple integrin receptors expressed on human gepatoma cells [J].Proc Soc Exp Biol Med, 1996;213: 71-79.
18 Stragies R, Osterkamp F, Zischinsky G, et al.Design and synthesis of a new class of selective integrin alpha5beta1 antagonists [J].Med Chem, 2007;50:3786-3794.
19 Pyrko P, Wang W, Markland FS, et al.The role of contortrostatin, a snake venom disintegrin, in the inhibition of tumor progression and prolongation of survival in a rodent glioma model [J].Neurosurg, 2005;103:526-537.
20 Sarray S, Delamarre E, Marvaldi J, et al.Lebectin and lebecetin, two C-type lectins from snake venom, inhibit alpha5beta1 and alphav-containing integrins [J].Matrix Biol, 2007; 26:306-313.
21 Golubkov V, Hawes D, Markland FS.Anti-angiogenic activity of contortrostatin, a disintegrin from Agkistrodon contortrix contortrix snake venom [J].Angiogenesis, 2003;6:213-224.
22 Swenson S, Costa F, Ernst W, et al.Contortrostatin, a snake venom disintegrin with anti-angiogenic and anti-tumor activity [J].Pathophysiol Haemost Thromb, 2005;34:169-176.
23 Kim SI, ChoiMM, Kim HS, et al.Inhibition of angiogenesis by salmosin expressed in vitro [J].Oncol Res, 2004;14:227-233.
24 Brando C, Marcinkiewicz C, Goldman B, et al.EC₃, a heterodimeric disintegrin from Echis carinatus, inhibits human and murine alpha4 integrin and attenuates lymphocyte infiltration of Langerhans islets in pancreas and salivary glands in nonobese diabetic mice [J].Biochem Biophys Res Commun, 2000;267: 413-417.
25 Marcinkiewicz C, Weinreb PH, Calvete JJ, et al.Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo [J].Cancer Res, 2003;63:2020-2023.
26 Kisiel DG, Calvete JJ, Katzhendler J, et al.Structural determinants of the selectivity of KTS-disintegrins for the alpha1beta1 integrin [J].FEBS Lett, 2004;577:478-482.27 Olfa KZ, José L, Salma D, et al.Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis [J].Lab Invest, 2005;85:1507-1516.
28 Hassan W, Al-Sergani H, Al Buraiki J, et al.Immediate and intermediate results of intracoronary stand-alone bolus administration of eptifibatide during coronary intervention(ICE) study [J].Am Heart J, 2007;154:345-351.
29 Swenson S, Costa F, Minea R, et al.Intravenou liposomal delivery of the snake venom disintegrin contortrostatin limits breast cancer progression [J].Mol Cancer Ther, 2004;3:499-511.
30 吴少瑜, 李志琴, 吴曙光.解离素-金属蛋白酶蛋白家族的基础与临床意义 [J].国外医学·生理、病理科学与临床分册, 2004;24:1001-1773.
31 Mochizuki S, Okada Y.ADAMs in cancer cell proliferation and progression [J].Cancer Sci, 2007;98:621-628.

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