Open AccessReversal by Two Dihydropyridine Compounds of Resistance to Multiple Anticancer Agents in Mouse P388 Leukemia in vivo and in vitro
Author(s) -
Kiue Akira,
Sano Tetsuro,
Naito Aya,
Inada Haruaki,
Suzuki Kenichi,
Okumura Masaya,
Kikuchi Junko,
Sato Shinichi,
Takano Hiroshi,
Kohno Kimitoshi,
Kuwano Michihiko
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb03346.x
Subject(s) - pharmacology , in vivo , vincristine , leukemia , in vitro , cell culture , vinblastine , vindesine , cancer research , biology , immunology , medicine , chemotherapy , biochemistry , cyclophosphamide , genetics , microbiology and biotechnology
We investigated whether two representative 1,4‐dihydropyridine derivatives, NK‐250 and NK‐252, could potentiate the antitumor activity of multiple anticancer agents including vincristine (VCR), vinblastine, vindesine and actinomycin D in drug‐resistant tumor cells and their parental drug‐sensitive tumor cells. NK‐250 and NK‐252 at 5–10 μ M almost completely reversed VCR resistance in cultured VCR‐resistant P388/VCR cells derived from the mouse drug‐sensitive P388/S leukemia cell line and also potentiated the cytocidal activity of VCR in drug‐sensitive P388/S cells. NK‐250 and NK‐252 at 1–10 μ M inhibited the photoaffinity labeling by [ 3 H]azidopine of the cell‐surface 170,000‐molecular‐weight P‐glycoprotein. In chemotherapeutic experiments with leukemia‐bearing mice, NK‐250 or NK‐252 was orally administered in combination with different drugs of the MDR phenotype administered intraperitoneally. The antitumor activity of the various combinations was found to be augmented in mice bearing P388/S‐ and P388/VCR‐leukemia. Among the combinations examined, the combination of NK‐250 and VCR was the most effective. These two 1,4‐dihydropyridines, NK‐250 and NK‐252, are unique compounds because they were effective not only in circumventing the drug resistance, but also in potentiating the action of antitumor drugs against drug‐sensitive tumors.