Cytotoxic and antitumor effect of fibrinogen-methotrexate conjugate.
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.
Boratyński
J
J
Department of Tumor Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. borat@immuno.iitd.pan.wroc.pl
Opolski
A
A
Wietrzyk
J
J
Górski
A
A
Radzikowski
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D005340:Fibrinogen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D012995:Solubility; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000922:Immunotoxins; C049996:fibrinogen-methotrexate conjugate; D005340:Fibrinogen; D008727:Methotrexate