Figure 1.

NRP‐1 up‐regulation in resistant MDA‐MB‐231 cells down‐regulates BCRP/ABCG2 and activates the integrin β3/FAK/NF‐κB_p65 survival pathway. Representative Western blots and densitometry quantification of five independent experiments (n = 5) for each tested protein indicated that MDA‐MB‐231 cells treated with 4xAC + 4xPAC caused a significant increase in NRP‐1 levels. However, there was a significant down‐regulation of BCRP/ABCG2 and TNFR2 in resistant cells to 4xAC and 4xAC + 4xPAC. NRP‐1 up‐regulation occurs synchronously with a significant increase in PI3K‐p110α in both 4xAC and 4xAC + 4xPAC. PTEN expression was significantly increased in 4xAC + 4xPAC resistant cells, which consequently caused a decrease in phosphorylated AKT‐S473. Resistance to either 4xAC or 4xAC + 4xPAC significantly increased integrin β3, p‐FAK, and p‐NF‐κB_p65. Cyclin B1 was significantly down‐regulated in resistant cells to 4xAC + 4xPAC, and DNMT1 was significantly down‐regulated in both 4xAC‐ and 4xAC + 4xPAC resistant cells. Individual protein band density quantification was normalized against their corresponding GAPDH bands. Data are presented as the mean relative density (arbitrary units, a.u.) ± SD (n = 5). *P < .05, significantly different from control cells; ANOVA and Tukey's post hoc test