EFFECTS OF MODULATORS OF MULTIDRUG-RESISTANCE ON THE EXPRESSION OF THE MDR1 GENE IN HUMAN KB CELLS IN CULTURE

The effect of four modulators of multidrug resistance (MDR) on the exp ression 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-quantitativ e assay based on mRNA reverse transcription coupled with polymerase ch ain 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 mu M of the modulators, MDR1 gene expre ssion was slightly but significantly decreased by two of them, quinine and cyclosporine A, whereas verapamil and S-9788 had very little effe ct on this parameter. The effect were more pronounced in the KB Al lin e than in the KB V1 line. The effect of quinine was studied over a lon ger time period (4-48 h) and was shown to be maximum at 24 h. These re sults favor the existence of a direct effect of same MDR reverters, es pecially quinine, on the expression of the MDR1 gene and could partial ly explain their modulating effect of MDR.