聚乙二醇修饰对α-苦瓜素抗肿瘤活性的影响
Effects of PEGylation on anti-tumor activity of α-momorcharin
作者：伍黎黎;沈富兵;刘敏;孟延发;
Author：
收稿日期： 年卷（期）页码：2011,26(01):-5-8
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：α-苦瓜素;聚乙二醇修饰;抗肿瘤活性
Key words：
基金项目：国家自然科学基金(批准号:30770232)
中文摘要
目的探讨苦瓜籽核糖体失活蛋白α-苦瓜素(α-MMC)经聚乙二醇(PEG)修饰后,其体外细胞毒性和体内抗肿瘤活性的变化。方法用MTT法测定α-MMC和PEG-α-MMC结合物对小鼠乳腺癌细胞EMT-6的抑制率;通过BALB/C小鼠模型研究药物对EMT-6细胞嫁接瘤生长的抑制作用。结果在相同的条件下,PEG-α-MMC结合物对体外培养的EMT-6细胞生长抑制效果相对α-MMC降低了30%,且两者对肿瘤细胞的毒性呈剂量和时间依赖性。PEG-α-MMC结合物的体内抗肿瘤活性比相同剂量的α-MMC增加约10%,且两者对肿瘤生长的抑制作用呈剂量依赖性。结论α-MMC经PEG修饰后,其体外抗肿瘤活性显著减低,而体内抗肿瘤活性增高,预示PEG-α-MMC结合物具备更好的抗肿瘤潜能。
参考文献
[1]Ren JS,Wang YP,Dong YC,et al.The N-glycosidase mecha-nism of ribosome-inactivating proteins implied by crystal struc-tures ofα-momorcharin[J].Structure,1994,2(1):7-16.
[2]Ng TB,Chan WY,Yeung HW.Proteins with abortifacient,ribo-some inactivating,immunomodulatory,antitumor and anti-AIDS activities from Cucurbitaceae plants[J].General Pharma-cology:The Vascular System,1992,23:575-590.
[3]Ng TB,Liub WK,Tsao SW,et al.Effect of trichosanthin and mo-morcharins on isolated rat hepatocytes[J].J Ethnopharmacology,1994,43:81-87.
[4]董惠钧,姜俊云,郑立军,等.蛋白药物聚乙二醇修饰技术研究进展[J].中国生化药物杂志,2009,30(3):199-203.
[5]An QX,Lei YF,Jia N,et al.Effect of site-directed PEGylationof trichosanthin on its biological activity,immunogenicity,andpharmacokinetics[J].Biomolec Engine,2007,24:643-649.
[6]Li ME,Chen YW,Liu ZY,et al.Anti-tumor activity and immu-nological modification of ribosome-inactivating protein(RIP)from Momordica charantia by covalent attachment of polyethyleneglycol[J].Acta Biochim Biophys Sin,2009,41:782-799.
[7]Fan JM,Luo J,Xu J,et al.Effects of recombinant MAP30 on cellproliferation and apoptosis of human colorectal carcinoma LoVocells[J].Mol Biotechnol,2008,39:79-86.
[8]Osborne CK,HobbsK,Clark GM.Effect of estrogensand antiestr-gens on growth of human breast cancer cell in athymic nude mice[J].Cancer Res,1985,45:584-590.
[9]孙海燕,胡家恕,汪俏梅.苦瓜的核糖体失活蛋白[J].细胞生物学杂志,2004,26(3):247-250.
[10]Bertholdo-Vargas LR,Martins JN,et al.Type 1 ribosome-in-activating proteins-Entomotoxic,oxidative and genotoxic actionon Anticarsia gemmatalis(Hübner)and Spodoptera frugiperda(J.E.Smith)(Lepidoptera:Noctuidae)[J].J Insect Physiolo-gy,2009,55:51-58.
[11]Yu DS,Peng P,Dharap SS,et al.Antitumor activity of poly(eth-ylene glycol)-camptothecin conjugate:the inhibition of tumorgrowth in vivo[J].J Contr Rel,2005,110:90-102.
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