Effects of modulators of multidrug resistance on the expression of the MDR1 gene on human KB cells in culture.
The effect of four modulators of multidrug resistance (MDR) on the expression of the MDR1 gene was studied in two resistant variants of the KB cell lines, KB V1 and KB A1. This was done using a semi-quantitative assay based on mRNA reverse transcription coupled with polymerase chain reaction of the cDNA obtained. An automatic DNA sequencer was used for the measurement of the fluorescent amplification products and the MDR1 signal was compared to that of the beta-actin gene of the cells. After 24 h incubation with 15 microM of the modulators, MDR1 gene expression was slightly but significantly decreased by two of them, quinine and cyclosporine A, whereas verapamil and S-9788 had very little effect on this parameter. The effect were more pronounced in the KB A1 line than in the KB V1 line. The effect of quinine was studied over a longer time period (4-48 h) and was shown to be maximum at 24 h. These results favor the existence of a direct effect of some MDR reverters, especially quinine, on the expression of the MDR1 gene and could partially explain their modulating effect of MDR.
Hu
Y P
YP
Institut Bergonié, Bordeaux, France.
Pourquier
P
P
Doignon
F
F
Crouzet
M
M
Robert
J
J
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019450:Genes, MDR / Q000187:drug effects*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D004317:Doxorubicin