Effect of ProVP16-I and -II on multidrug-resistant MOVP-3 cells. The VP16-resistant MOVP-3 cell line was analyzed for resistance against VP16-induced cytotoxicity (A), cross resistance to MDR-1 drugs, which are known substrates for p-glycoprotein (B), and functional MDR-1—mediated substrate efflux (C). Resistance of MOVP-3 cells against VP16 was calculated from IC50 concentrations according to IC50MOVP-3 ÷ IC50Molt-3 (n = 3) and results compared with effects observed with ProVP16-I and -II (A). Differential findings between Molt-3 and MOVP-3 cells obtained with VP16 were statistically significant (P < .001) in contrast to ProVP16-I and -II (P > .05). (B) Cross resistance of MOVP-3 cells against MDR-1 drugs (doxorubicin, melphalan, vinblastine, and paclitaxel) was calculated from IC50 values (n = 3) as described in Figure 4B. Results for non—MDR-1 drugs (MTX, 5-FU, genistein, calicheamicin θ, ProVP16-I) are shown as controls. Differential findings for MDR-1 drugs between MOVP-3 and Molt-3 cells were all statistically significant (P < .01) in contrast to non—MDR-1 drugs (P > .05). (C) MDR-1—mediated substrate efflux by MOVP-3 cells (left) and Kelly cells (right) was demonstrated using the JC-1 assay. Inhibition of MDR-1 was determined using 3 × 10-4 M ProVP16-I and ProVP16-II and compared with equivalent amounts of VP16 and PBS controls. Histograms represent a typical result of 3 independent experiments.
