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


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.
Ying
W
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Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, California 92037.
Martineau
D
D
Beitz
J
J
Lappi
D A
DA
Baird
A
A
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D000922:Immunotoxins; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010940:Plant Proteins / Q000008:administration & dosage*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins