Antagonistic effect of amphotericin B on carboplatin antitumor activity in human osteosarcoma xenografts.
Amphotericin B (AmB), a polyene antifungal antibiotic, has been shown to potentiate the cytotoxic effect of different chemotherapeutic drugs in vivo and in vitro. The purpose of this study was to determine whether AmB could enhance the carboplatin antitumor activity in a human osteosarcoma xenograft model. Nude mice, bearing s.c. transplanted osteosarcoma xenografts, received i.p. an injection of AmB (5 mg/kg) 6 h prior to carboplatin (20 mg/kg) or each of the drugs separately. The effect of treatment was assessed by analyzing tumor growth delay and T/C ratio. Carboplatin clearly reduced tumor growth when administered alone. However, an unexpected interaction was seen where AmB significantly decreased the antitumor effect of carboplatin. The present results contradict some earlier in vitro studies and indicate the complexity of this interaction in vivo. Hence, it seems that interactive phenomena in one experimental model, and especially with regard to AmB, cannot be universally applied to all experimental situations.
Crnalic
S
S
Department of Orthopaedics, Umeá University Hospital, Sweden.
Bergström
P
P
Löfvenberg
R
R
Henriksson
R
R
Broström
L A
LA
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000188:drug therapy*; D014183:Transplantation, Heterologous
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000666:Amphotericin B; D016190:Carboplatin