Anti-B16-F10 melanoma activity of a basic fibroblast growth factor-saporin mitotoxin.

Abstract

The authors attached basic fibroblast growth factor (FGF-2), a growth factor for numerous tumors and normal cell types, to saporin (SAP), a ribosome-inactivating protein isolated from the plant Saponaria officinalis. The conjugate (FGF-SAP) then was tested for antitumor activity using B16-F10 melanoma cells. This rapidly growing murine melanoma cell line has been used classically as a model to screen antitumor agents. B16-F10 cells in culture were used for in vitro experiments or introduced into C57BL/6 mice to demonstrate the in vivo antitumor activities of FGF-SAP. FGF-SAP was found to be an extremely effective cytocidal agent in vitro with an ED50 of 30-60 pM. The effects were specific for FGF-2 receptors, as shown by the ability of FGF-2 to block FGF-SAP action. In the in vivo models, FGF-SAP was found to increase survival time, inhibit tumor growth, and decrease metastases. The authors conclude that this mitotoxin has potent in vitro and in vivo effects on B16-F10 cells, supporting the hypothesis that ligand-mediated cytotoxicity can control tumor growth.