REVERSAL OF C1300 MURINE NEUROBLASTOMA MULTIDRUG-RESISTANCE BY CREMOPHOREL, A SOLVENT FOR CYCLOSPORINE-A

被引:12
作者
CHERVINSKY, DS
BRECHER, ML
BAKER, RM
HOELCLE, MJ
TEBBI, CK
机构
[1] ROSWELL PK CANC INST, DEPT EXPTL THERAPEUT, BUFFALO, NY 14263 USA
[2] CHILDRENS HOSP BUFFALO, BUFFALO, NY 14222 USA
[3] SUNY Buffalo, DEPT PEDIAT, BUFFALO, NY 14214 USA
[4] ST JOSEPHS HOSP, TAMPA, FL 33677 USA
来源
CANCER BIOTHERAPY | 1993年 / 8卷 / 01期
关键词
D O I
10.1089/cbr.1993.8.67
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We previously developed a homoharringtonine resistant C-1300 neuroblastoma cell line with cross-resistance to adriamycin and increased levels of p-glycoprotein, and showed that drug resistance could be reversed in this cell line by cyclosporin A. The present study shows that cremophor EL, a parenteral vehicle for cyclosporin A, can also completely reverse this multidrug resistance in a clonogenic assay system. Cremophor EL incubated with resistant cells for up to six days did not. reduce levels of p-glycoprotein. Intracellular homoharringtonine analysis using HPLC revealed increased drug accumulation in resistant cells treated with cremophor EL. The increased drug level was not due to blocking of drug efflux commonly seen in other multidrug resistant models. The data suggest that resistance modulation with cyclosporin A should be interpreted with caution when cremophor EL is a solvent. Our work suggests cremophor EL, a relatively nontoxic. lipophylic solvent, may have a direct effect on membrane permeability, although other mechanisms cannot be ruled out.
引用
收藏
页码:67 / 75
页数:9
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