Enhancement of cisplatin (DDP) antitumor activity by 3-aminobenzamide in rat ovarian tumors sensitive and resistant to DDP in vivo.
A cisplatin (DDP)-resistant rat ovarian tumor cell line (O-342/DDP) and its parental sensitive counterpart (O-342) were used to investigate the combination effect of DDP plus 3-aminobenzamide (3-AB), an inhibitor of adenosine diphosphate ribose transferase (ADPRT). Treatment with six doses of DDP in NMRI nude mice bearing O-342/DDP produced an increase in mean survival of only 1 day over that of controls (P less than 0.05). The addition of nontoxic doses of 3-AB (5 mM/kg x 6) increased the mean survival to 6.4 days compared with that obtained with DDP treatment alone (P less than 0.001). In the sensitive ovarian tumor line (O-342), the combination effect of DDP plus 3-AB was even more impressive: simultaneous treatment of NMRI nude mice bearing O-342 with three doses of DDP plus 3-AB increased the mean survival by 2 weeks and the median survival by 3 weeks over that achieved with DDP treatment alone. Possible mechanisms involved in the potentiation of DDP activity and the possible clinical potential of this combination are discussed.
Chen
G
G
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Zeller
W J
WJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D004357:Drug Synergism; D005038:Ethylnitrosourea; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051381:Rats
D001549:Benzamides; C025160:3-aminobenzamide; D005038:Ethylnitrosourea; D002945:Cisplatin