碱性成纤维细胞生长因子-皂草毒素有丝分裂毒素在体内外的抗肿瘤活性

Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo.

作者信息

Beitz J G, Davol P, Clark J W, Kato J, Medina M, Frackelton A R, Lappi D A, Baird A, Calabresi P

机构信息

Roger Williams Cancer Center, Brown University, Providence, Rhode Island 02908.

出版信息

Cancer Res. 1992 Jan 1;52(1):227-30.

PMID:1309225

Abstract

Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome-inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed.

摘要

许多癌细胞系表达碱性成纤维细胞生长因子（FGF）受体，使其成为基于FGF的细胞毒性化合物递送的潜在靶点。为此，我们研究了一种新型线粒体毒素——成纤维细胞生长因子-皂草素（FGF-SAP）的抗肿瘤活性，它是FGF与核糖体失活蛋白皂草素的偶联物。在体外，FGF-SAP对表达FGF受体的人黑色素瘤、畸胎瘤和神经母细胞瘤细胞具有细胞毒性。以各种给药方案经静脉注射FGF-SAP治疗的小鼠，显示出显著的肿瘤生长抑制，且毒性极小。因此，FGF-SAP似乎是一种耐受性良好且有效的抗肿瘤药物。本文还讨论了FGF靶向细胞毒性的潜力。