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Evidence for reversal of multidrug resistance by quinine in LR73 cells without alteration of nuclear pirarubicin uptake and down‐regulation of mdr 1 gene expression
Author(s) -
Belhoussine Rajae,
Morjani Hamid,
Lahlil Rachid,
Manfait Michel
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971114)73:4<600::aid-ijc23>3.0.co;2-b
Subject(s) - verapamil , quinine , multiple drug resistance , pirarubicin , cell culture , biology , chinese hamster ovary cell , p glycoprotein , gene expression , doxorubicin , pharmacology , microbiology and biotechnology , drug resistance , chemistry , gene , chemotherapy , biochemistry , immunology , genetics , organic chemistry , malaria , calcium
Confocal laser microspectrofluorometry was used to investigate restoration of nuclear pirarubicin (THP‐DOX) accumulation and sensitivity by verapamil, quinine and S9788 in 2 variants of the Chinese hamster ovary cell lines LR73, selected for resistance to doxorubicin (LR73D) or transfected with the mdr 1 gene (LR73R). The 2 resistant cell lines present a multidrug‐resistance phenotype (MDR). Verapamil and S9788, which interact with P‐glycoprotein (P‐gp), were able to restore nuclear THP‐DOX accumulation in LR73R and LR73D cells to a level equivalent to that in sensitive cells. On the other hand, quinine was unable to increase nuclear THP‐DOX accumulation significantly even at a concentration of 50 μM. All modulators completely restored THP‐DOX sensitivity in resistant cell lines. Our results also show that verapamil and S9788 allow high nuclear drug accumulation, whereas quinine did not affect nuclear accumulation. The effect of quinine on the mdr 1 gene expression was determined by the use of reverse transcription coupled with polymerase chain reaction. After a 2 hr treatment with 20 μM of quinine, mdr 1 gene expression increased slightly. Int. J. Cancer 73:600–606, 1997. © 1997 Wiley‐Liss, Inc.