Swenson Stephen, Costa Fritz, Ernst William, Fujii Gary, Markland Francis S
University of Southern California, Keck School of Medicine, Los Angeles, Calif. 90033, USA.
Pathophysiol Haemost Thromb. 2005;34(4-5):169-76. doi: 10.1159/000092418.
Disintegrins are soluble peptides found in snake venom. They bind to Arg-Gly-Asp (RGD)-responsive integrins with high affinity (nM range) and block integrin function. Contortrostatin (CN), the disintegrin from southern copperhead venom, is a homodimer with a molecular weight of 13,500. Each chain contains 65 amino acids with an Arg-Gly-Asp motif. CN has anti-invasive and anti-adhesive activity on tumor cells and endothelial cells in vitro, and binds to integrins alphavbeta3, alphavbeta5, and/or alpha5beta1. In vivo studies using the human metastatic breast cancer cell line MDA-MB-435, in an orthotopic xenograft model in nude mice, revealed that CN has potent anti-tumor and anti-angiogenic activity. Recent studies have employed an intravenous liposomal delivery procedure. Liposomal delivery of CN has also been shown to provide effective in vivo anti-tumor and anti-angiogenic activity in a human ovarian cancer animal model.
去整合素是存在于蛇毒中的可溶性肽。它们以高亲和力（纳摩尔范围）与Arg-Gly-Asp（RGD）反应性整合素结合，并阻断整合素功能。扭曲毒素（CN）是来自南铜头蝮蛇毒液的去整合素，是一种分子量为13500的同二聚体。每条链含有65个氨基酸，并具有Arg-Gly-Asp基序。CN在体外对肿瘤细胞和内皮细胞具有抗侵袭和抗粘附活性，并与整合素αvβ3、αvβ5和/或α5β1结合。在裸鼠原位异种移植模型中使用人转移性乳腺癌细胞系MDA-MB-435进行的体内研究表明，CN具有强大的抗肿瘤和抗血管生成活性。最近的研究采用了静脉脂质体递送方法。在人卵巢癌动物模型中，脂质体递送CN也已显示出有效的体内抗肿瘤和抗血管生成活性。
