Circumvention of doxorubicin resistance in multi-drug resistant human leukaemia and lung cancer cells by the pure antioestrogen ICI 164384

X. F. Hu, G. Nadalin, M. De Luise, T. J. Martin, A. Wakeling, R. Huggins, J. R. Zalcberg

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ICI 164384, a new steroidal antioestrogen, entirely devoid of oestrogenic activity, modulates doxorubicin resistance in vitro. At non-cytotoxic concentrations, ICI 164384 potentiated the cytotoxicity of doxorubicin in a dose-dependent manner in both the classical multi-drug resistant (MDR) human leukaemia cell lines CEM/VLB 100 and CEM/VLB 1000 and the human small cell lung cancer cell line H69 LX4. ICI 164384 had no effect on the two respective parental cell lines, CEM/CCRF and H69 P. None of these cell lines expressed the oestrogen receptor. In comparative studies at concentrations ranging from 1.25 to 10 μmol/l, ICI 164384 was significantly more effective (1.2-6-fold) than tamoxifen in reducing the IC50 of doxorubicin in the CEM/VLB 100 line. In resistant cells, ICI 164384 increased 3H-daunomycin accumulation in a dose-dependent manner and was significantly more effective than tamoxifen at concentrations ranging from 2.5 to 10 μmol/l. ICI 164384 reduced the efflux of daunomycin from resistant cells more effectively than tamoxifen. These studies suggest that ICI 164384 is an effective modulator of MDR.

Original languageEnglish
Pages (from-to)773-777
Number of pages5
JournalEuropean Journal of Cancer and Clinical Oncology
Issue number6
Publication statusPublished - 1 Jan 1991
Externally publishedYes

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