A novel plasmin-inhibitor inhibits the growth of human tumor xenografts and decreases metastasis number.
The novel plasmin inhibitor YO-2, which also exerts an apoptosis-inducing effect on various human tumor cell cultures, was examined regarding its tumor growth inhibitory and antimetastatic action. The tumor growth inhibitory effect of YO-2 was studied using HT-29 human colon carcinoma, HT-18 human melanoma and HT-58 human B cell lymphoma inoculated as xenografts into immuno-deprived mice. Antimetastatic activity was tested on the B16 mouse melanoma muscle-lung model. YO-2 inhibited the growth of all xenografts in the range of 40-50%, when administered s.c. at a dose of 2.0 mg/kg (HT-29, HT-58) or orally at a dose of 0.4 mg/kg (HT-18). YO-2 decreased the number of lung metastasis found in mice inoculated i.m. with B16 melanoma, 4 mg/kg being the most effective. Since YO-2 is the only plasmin inhibitor having antihemorrhagic and also antitumor effect, this compound could be rationally used in combination therapy of neoplastic disease, especially when hemorrhage aggravates the course of the disease.
Szende
Béla
B
1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Molecular Pathology Research Group of Hungarian Academy of Sciences, Budapest, Hungary.
Okada
Yoshio
Y
Tsuda
Yuko
Y
Horvath
Aniko
A
Bökönyi
Gyöngyi
G
Okamoto
Shosuke
S
Wanaka
Keiko
K
Kéri
György
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006801:Humans; D016867:Immunocompromised Host; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004151:Dipeptides; D004791:Enzyme Inhibitors; C419205:YO 2 compound; D005341:Fibrinolysin