维拉帕米可增强4'-表阿霉素在大鼠肝癌细胞系及对4'-表阿霉素耐药的亚系中的细胞毒性。

Verapamil potentiates 4'-epidoxorubicin cytotoxicity in a rat hepatoma cell line and in a substrain resistant to 4'-epidoxorubicin.

作者信息

Hall K S, Endresen L, Rugstad H E

机构信息

Department of Clinical Pharmacology, University of Oslo, Rikshospitalet, Norway.

出版信息

Pharmacol Toxicol. 1990 Nov;67(5):402-5. doi: 10.1111/j.1600-0773.1990.tb00852.x.

DOI:10.1111/j.1600-0773.1990.tb00852.x

PMID:1965744

Abstract

We have examined the influence of verapamil (VP) on the in vitro effect of 4'-epidoxorubicin (Epi-A) in a rat hepatocarcinoma cell line (MHlCl) and in an Epi-A resistant substrain. A VP concentration of 500 ng/ml (1.1 mumol/l) markedly potentiated the cytotoxic effect of Epi-A in the parent line. The resistant cells grow at an Epi-A concentration of 7500 ng/ml (12.9 mumol/l). This is approximately 15-fold higher than the concentration tolerated by parental cells. In these cells VP reversed the acquired resistance to Epi-A in a concentration dependent manner; thus, a concentration in the range of 500-750 ng/ml (1.1-1.7 mumol/l) of VP restored the sensitivity to Epi-A in the resistant cells. Our results demonstrate that VP increases the sensitivity to Epi-A in hepatocarcinoma cells never exposed to this drug, as well as in hepatocarcinoma cells with acquired Epi-A resistance.

摘要

我们研究了维拉帕米（VP）对4'-表阿霉素（Epi-A）在大鼠肝癌细胞系（MHlCl）及Epi-A耐药亚系中的体外作用的影响。500 ng/ml（1.1 μmol/l）的VP浓度显著增强了Epi-A对亲代细胞系的细胞毒性作用。耐药细胞在7500 ng/ml（12.9 μmol/l）的Epi-A浓度下生长。这大约比亲代细胞耐受浓度高15倍。在这些细胞中，VP以浓度依赖的方式逆转了对Epi-A获得性耐药；因此，500 - 750 ng/ml（1.1 - 1.7 μmol/l）范围内的VP浓度可恢复耐药细胞对Epi-A的敏感性。我们的结果表明，VP增加了从未接触过该药物的肝癌细胞以及具有获得性Epi-A耐药的肝癌细胞对Epi-A的敏感性。