1. Cytotoxic and antitumor effect of fibrinogen-methotrexate conjugate.
- Author
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Boratyński J, Opolski A, Wietrzyk J, Górski A, and Radzikowski C
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Fibrinogen administration & dosage, Fibrinogen therapeutic use, Fibrinogen toxicity, Humans, Immunotoxins administration & dosage, Inhibitory Concentration 50, Injections, Intraperitoneal, Leukemia P388 drug therapy, Male, Methotrexate administration & dosage, Methotrexate therapeutic use, Methotrexate toxicity, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Neoplasm Transplantation, Solubility, Tumor Cells, Cultured drug effects, Antineoplastic Agents therapeutic use, Antineoplastic Agents toxicity, Fibrinogen analogs & derivatives, Immunotoxins therapeutic use, Immunotoxins toxicity, Methotrexate analogs & derivatives
- Abstract
In this paper we describe the chemical procedure of fibrinogen-methotrexate (F-MTX) conjugate preparation and its in vitro and in vivo antitumor activity. F-MTX conjugates were synthesized in reaction of fibrinogen with MTX N-hydroxysuccynimide ester. The conjugates were not cross-linked and were soluble in water. The results of the in vitro and in vivo studies have shown: (1) a lower in vitro cytotoxicity of the F-MTX conjugate as compared with MTX alone; (2) a significantly higher in vivo antitumor activity of the F-MTX conjugate in mice with P388 leukemia as compared with MTX alone; (3) a significantly increased in vivo lethal toxicity of F-MTX as compared with MTX. The results suggest the therapeutic utility of the fibrinogen-methotrexate conjugate and the usefulness of fibrinogen as a chemotherapeutic drug carrier. However, a new effort in the preparation of F-MTX conjugate should be made to decrease its in vivo toxicity. more...
- Published
- 2000
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