Figure 3

P-gp inhibition and MDR chemosensitization. In (A), KB-V1 MDR cells were incubated at 37°C for 1 hr with 5 μg/ml doxorubicin alone or in presence of 2.5 μg/ml verapamil or 25 μg/ml RDS 1984. After washing the cells were reincubated again in identical conditions and doxorubicin efflux/retention were analysed in confocal microscopy after 1 h (panel a-c) and 3 hrs (panel d-f). The natural efflux of doxorubicin P-gp mediated is shown in panel a and d, while the doxorubicin retention due to the P-gp drug transport inhibition exerted by verapamil and RDS 1984 is shown in panel b-c (1 h incubation) or e-f (3 hrs incubation). In (B), dose-response cytotoxicity to vinblastine in CEM-VBL100 MDR cells in presence of verapamil (2.5 μg/ml) or 10 μg/ml of the IINs RDS 1974, RDS 1981, RDS 1983 and RDS 1984 is shown. The values (formazan absorbance at 440 nm in ELISA reader) were calculated as % of control cells cultured in presence of IINs only or verapamil. The mean of triplicate measurements is shown; the SD was < 15% of each single value.