Antimetastatic activity of adriamycin in combinations with proteinase inhibitors in mice.
The antimetastatic activity of adriamycin in combination with proteinase inhibitors was investigated in mice bearing the metastatic tumors L1210 leukemia, Lewis lung carcinoma or M5076 sarcoma. Leupeptin, a cathepsin B inhibitor, when administered as a single agent was devoid of antimetastatic activity but some therapeutic activity was noted in mice with Lewis lung carcinoma when the agent was administered in combination with adriamycin. Pepstatin A, a cathepsin D inhibitor, had no effect as a single agent in mice with L1210 leukemia but displayed some antimetastatic activity in mice with Lewis lung carcinoma. In mice with M5076 sarcoma the combination of pepstatin A and adriamycin resulted in antimetastatic activity significantly greater than that observed with each agent alone. These results suggest that combinations of proteinase inhibitors with antitumor drugs such as adriamycin, might result in more effective antimetastatic treatment.
Leto
G
G
Institute of Pharmacology, Faculty of Medicine, University of Palermo, Italy.
Tumminello
F M
FM
Gebbia
N
N
Woynarowska
B
B
Bernacki
R J
RJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002401:Cathepsin B / Q000502:physiology; D002402:Cathepsin D / Q000502:physiology; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D007976:Leupeptins / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage*; D010436:Pepstatins / Q000008:administration & dosage*; D011480:Protease Inhibitors / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D007976:Leupeptins; D009842:Oligopeptides; D010436:Pepstatins; D011480:Protease Inhibitors; C014195:Streptomyces pepsin inhibitor; D004317:Doxorubicin; D002401:Cathepsin B; D002402:Cathepsin D; C032854:leupeptin; C031375:pepstatin