Fiche publication
Date publication
novembre 1997
Journal
International journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid
,
Dr LAHLIL Rachid
Tous les auteurs :
Belhoussine R, Morjani H, Lahlil R, Manfait M
Lien Pubmed
Résumé
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 mdr1 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 microM. 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 mdr1 gene expression was determined by the use of reverse transcription coupled with polymerase chain reaction. After a 2 hr treatment with 20 microM of quinine, mdr1 gene expression increased slightly.
Mots clés
Animals, CHO Cells, drug effects, Cell Nucleus, metabolism, Cricetinae, Doxorubicin, analogs & derivatives, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Gene Expression Regulation, drug effects, Genes, MDR, drug effects, P-Glycoprotein, drug effects, Piperidines, pharmacology, Quinine, pharmacology, Triazines, pharmacology, Verapamil, pharmacology
Référence
Int. J. Cancer. 1997 Nov;73(4):600-6
