Superiority of cyclosporin A over PSC-833 in enhancement of VP-16 efficacy in murine tumors in vivo.
PSC-833, a non immunosuppressive analogue of cyclosporin A, is an effective modulator of the multidrug-resistant tumor phenotype. Since both PSC-833 and cyclosporin A also enhance the cytotoxicity of VP-16 against drug sensitive L1210 leukemia cells in vitro we compared these agents as modulators of VP-16 efficacy in vivo. Compared to VP-16 treatment alone both PSC-833 and cyclosporin A significantly altered the survival of L1210 leukemia-bearing BDF/1 mice and Lewis lung carcinoma-bearing C57/B1 mice. Cyclosporin A enhanced VP-16 efficacy whereas PSC-833 impaired VP-16 efficacy against these murine tumors. Possible reasons for these disparate effects are discussed.
Slater
L M
LM
Department of Medicine, University of California, Irvine 92717, USA.
Sweet
P
P
Stupecky
M
M
Osann
K
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use*; D004357:Drug Synergism; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015996:Survival Rate; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D005047:Etoposide; D016572:Cyclosporine; C070272:valspodar