Figure 6.

The ABC drug efflux transporter ABCG2 is upregulated by collagen type 1 (COL1) via the MAPK pathway in MDA-MB-231 cells. (a) Functional ABCG2 activity assay using the ABCG2 substrate pheophorbide A and its inhibition by SCH772984 which is visible in scrambled (sc) cells in presence of COL1 and in integrin β₁-knockdown (ITGB1-kd) cells The effect of 24 h incubation of SCH772984 (1 µM) was shown to reduce expression of ABCG2 in sc, COL1-treated and ITGB1-kd cells in Western blot experiments using GAPDH as loading control (b) (in both figures n = at least 3 biological samples). (c) Analysis of the inhibitory properties of SCH77284 itself in ABCG2 overexpressing MDCK II BCRP cells revealed no intrinsic inhibitory effect in comparison to BCRP inhibitor Ko143 at all up to the concentration of 1 µM used (n = at least 3 biological samples). Statistical analysis was performed via unpaired t-test (* p < 0.05; ** p < 0.01; *** p < 0.001).