In:
International Journal of Cancer, Wiley, Vol. 50, No. 4 ( 1992-02-20), p. 593-597
Abstract:
Cyclosporin A (CsA, Sandimmune) is known to reverse P‐glycoprotein(P‐gp 170)‐mediated multidrug resistance as efficiently as other prototype compounds of resistance modifiers. The immunosuppressive activity and nephrotoxicity of CsA, however, may limit its clinical use. PSC‐833, a new cyclosporine, exerts a similar resistance‐modifying activity but lacks toxicity or immunosuppressive activity. We have tested its potency in vitro and in vivo on the L1210 leukemia cell line transfected with a full‐length cDNA copy of the human mdr I gene, which showed a stable 30‐fold resistance towards adriamycin as compared to the parental cell line. In vitro growth of the transfected cell was unchanged. In vivo growth was less aggressive; the survival time of inoculated mice was prolonged. In vitro , PSC‐833 was at least as potent as CsA or verapamil in reversing multidrug resistance. In vivo , the drug‐resistant L1210 leukemia was completely unresponsive to i.v. monotherapy with adriamycin at its maximum tolerated dose (MTD). PSC‐833 enhanced the activity and toxicity of adriamycin. The MTD of adriamycin was about 3 times lower than when given alone. On this basis, the MTD of i.v. adriamycin in combination with oral PSC‐833 successfully overcame refractoriness to treatment. Survival times of the mice were considerably prolonged and even some cures of leukemic mice occurred.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
DOI:
10.1002/ijc.2910500418
Language:
English
Publisher:
Wiley
Publication Date:
1992
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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