@entity620 increases drug accumulation and reverses @entity1891 resistance of @entity1 non-small-cell XXXX cells.

@entity1 @entity632 @entity756 @entity620 @entity1855 @entity2 @entity900 @entity4316 @entity2879 @entity1891 @entity460 @entity3812 @entity5713
A @entity1 @entity2 @entity756 subline with acquired resistance to @entity1891 (VCR), a chemotherapeutic agent, was established with incremental increases of the drug. The resistant @entity756 subline ( @entity756 /VCR) shows a 12-fold increase in resistance to VCR and a unique cross-resistance pattern: high cross-resistance to the potent VCR analogue @entity3812 (6.9-fold) and @entity5713 (2.5-fold); lower cross-resistance to @entity4316 (1.8-fold), @entity900 (1.2-fold) and @entity632 (1.3-fold) and a sensitivity to melphalan and @entity2879 which is similar to that of the parental cell line. A reduced accumulation of VCR in the resistant cells was demonstrated. Interestingly, the VCR resistance of the @entity756 /VCR cell line was partially reversed by @entity620 , and the drug uptake was enhanced. In contrast, @entity620 had no effect on drug tolerance and drug accumulation was not observed in either @entity756 parental cells or known multidrug-resistant (MDR) cells, suggesting that VCR resistance in @entity756 /VCR cells results essentially from reduced drug accumulation. It is worth noting that, whereas reduced drug accumulation in the @entity756 /VCR cells was susceptible to modulation by @entity620 , the increased efflux rate characteristic of the resistant cells was not. Further, there was a higher efflux rate in resistant cells than in parental cells. DNA Southern- and RNA Northern-blot hybridization analyses indicate that @entity756 /VCR cells do not contain amplified mdr genes or overexpress P-glycoprotein. In addition, the @entity460 -channel blocker @entity1855 , which acts as a competitive inhibitor of drug binding and efflux, did not affect the resistant phenotype of @entity756 /VCR cells. These findings suggest an @entity620 -sensitive drug uptake mechanism which is important in mediating VCR resistance per se in @entity1 @entity2 cells; this differs from the P-glycoprotein-mediated MDR mechanism.
