The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

摘要: Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular is an feature of solid known to present significant barriers permeation in tumours. Given this barrier, do mechanisms such as P-glycoprotein (P-gp) contribute significantly resistance? To address question, the multicellular tumour spheroid (MCTS) model was used examine influence P-gp on distribution tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7WT cells or drug-resistant, P-gp-expressing derivative MCF7Adr. Confocal microscopy measure time courses patterns three fluorescent compounds; calcein-AM, rhodamine123 BODIPY-taxol. These compounds chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence chemically dissimilar. For example, BODIPY-taxol rhodamine 123 showed accumulation distributed extensively throughout TSWT, whereas calcein-AM restricted outermost layers. The presence TSAdr resulted negligible accumulation, regardless compound. Moreover, inhibition by nicardipine restored intracellular levels observed TSWT. results demonstrate effectiveness modulating models. However, penetration agents tissue strongly determined physico-chemical properties individual compounds.