蝎毒多肽提取物抗肿瘤血管生成作用的实验研究  

Polypeptide extract from scorpion venom inhibits angiogenesis and angiogenesis-dependent tumor growth

作　　者：张维东[1] 崔亚洲[2] 姚成芳[1] 贾青[1] 宋守琴[1] 王朝霞[1] 董强[1] 

机构地区：[1]山东省医学科学院基础医学研究所,山东济南250062 [2]山东省医药生物技术研究中心,山东济南250062

出　　处：《中国药理学通报》2005年第6期708-711,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30371841);山东省科技发展计划项目(No031050116)

摘　　要：目的探讨东亚钳蝎蝎毒的多肽提取物PESV的抗血管生成活性和对肿瘤生长的抑制作用。方法①用不同浓度的PESV(4～20mg·L-1)作用于人脐静脉内皮细胞(HUVEC),采用BrdU参入的ELISA法观察HUVEC增殖活性和凋亡水平变化,流式细胞术检测凋亡细胞比例,免疫组化法检测Bal和Bax表达。②观察PESV对鸡胚尿囊膜(CAM)新生血管生成的影响。③皮下注射PESV(0.3mg·kg-1),观察对S180肉瘤和H22肝癌荷瘤小鼠肿瘤生长、肿瘤血管生成和血管生成因子(VEGF和bFGF)表达的影响。结果①体外实验显示,PESV在8～20mg·L-1范围明显抑制HUVEC的增殖活性(与对照组比较,P<0.01),而对乳腺癌细胞MDAMB231的增殖无影响;PESV作用后HUVEC凋亡细胞比例较对照组增加,P<0.05,Bax表达增加;Bcl2表达降低。②0.5mg/CAM和0.8mg/CAM的PESV能明显抑制CAM新生血管的形成。③体内实验显示PESV能明显抑制小鼠S180肉瘤和H22肝癌的肿瘤生长和血管生成水平,并降低肿瘤组织内血管生成相关因子VEGF和bFGF的表达。结论PESV具有良好的体内和体外抗肿瘤血管生成活性,并籍此抑制肿瘤的生长。Aim The purpose of this study was to evaluate the anti-angiogenic and anti-tumor activities of PESV, a peptide extract from scorpion venom, and to elucidate its mechanism of action. Methods ① HUVEC was used to test the anti-angiogenic effect of PESV in vitro. Cell proliferation was detected by the BrdU cell incorporation ELISA. Apoptotic cell percentage determined by flow cytometry; ② CAM assay was used to determine the effect of PESV on neovascularization in vivo; ③ The mice with S180 sarcoma or H22 hepatoma were injected with PESV at 3 mg·kg -1. Tumor growth, the number of blood vessels and the expression of angiogenic factors were observed. Results ① PESV exhibited potent anti-proliferative and apoptosis-induced activity against HUVEC, but showed no sighificant effect on tumor cell line MDA-MB-231. ② CAM assay showed inhibition of neovascularization by PESV. ③ Systemic administration of PESV suppressed S180 sarcoma and H22 hepatoma tumor growth in mice. Immunohistochemical examination of tumors showed a significant decrease in the number of blood vessel and the reduced expression of VEGF and bFGF. Conclusion The results suggest that PESV contains potent anti-angiogenic and anti-tumor molecule, and its component should be further analyzed.

关 键 词：蝎毒 血管生成 鸡胚尿囊膜 肉瘤 肝癌 

分 类 号：R-332[医药卫生] R329.25