Kinetic analysis in living cells of the inhibition of the @entity1262 -mediated efflux of @entity8253 by XXXX .

@entity632 @entity1262 @entity7765 @entity8253 @entity7324 @entity5699 @entity17074 @entity8779 @entity4349 @entity1206 @entity6007 @entity1891 @entity5713
Cells that overexpress the @entity1262 gene have decreased steady-state accumulation and increased efflux of many anticancer drugs including @entity8253 and @entity17074 . The mechanism(s) of @entity1262 -mediated efflux of drugs is (are) still poorly understood. In an attempt to identify mechanism(s) by which multidrug resistance can be circumvented, the cellular accumulation has been examined of @entity7765 , @entity632 and @entity8779 alone and in conjunction with four vinca alkaloid derivatives-- @entity5713 , @entity1206 , @entity7324 and @entity1891 . The present study was performed using a spectrofluorometric method with which it is possible to follow continuously the uptake and release of fluorescent molecules by living cells, as the incubation of the cells with the drug proceeds. @entity6007 K562 cell lines were used. It has been shown that the @entity1262 -mediated efflux of these three @entity8253 can be inhibited by @entity17074 derivatives. At pH 7.2, 50% of the @entity1262 -mediated efflux of @entity5699 and @entity8779 was inhibited by about 40 +/- 10 microM @entity5713 and that of @entity7765 by 10 +/- 2 microM @entity5713 . The @entity5713 concentration required to inhibit 50% of the active efflux of these @entity8253 did not depend on the @entity4349 concentrations used, indicating that the inhibition was non competitive. The ability of @entity1206 , @entity1891 and @entity7324 to inhibit the active efflux of @entity7765 was also checked; 15 +/- 3 microM @entity1206 are required to inhibit 50% of the active efflux but at concentrations lower than 100 microM, neither @entity1891 nor @entity7324 were able to inhibit this efflux, indicating that the @entity17074 compounds which are the most efficient are the most lipophilic. For the four @entity17074 , the concentration required to inhibit 50% of the efflux was lower as the pH was higher. A detailed kinetics analysis of the @entity1262 -mediated efflux of @entity7765 in the presence of @entity5713 indicates a non competitive inhibition with K(I) = 12 +/- 2 microM.
