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

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Abstract
Background. The authors attached basic fibroblast growth factor (FGF‐2), a growth factor for numerous tumors and normal cell types, to saporin (SAP), a ribosomeinactivating 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. Methods. 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. Results. 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. Conclusions. 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.