Figure 3 : UIC2 and 5D3 labeling in ABCB1-(SW620 Ad300) and ABCG2-overexpressing (S1M1 80) resistant cells, respectively, suggesting interaction between volasertib and the two transporters.


(A) A typical UIC2 and 5D3 shift exhibited by ABCB1 (PSC833) and ABCG2 (Ko143) inhibitor, respectively. The solid line represents UIC2/5D3 binding of untreated cells (native staining) and dotted line for cells incubated with 1 μM PSC833 and 200 nM Ko143, respectively. The shaded histogram represents the background fluorescent signal upon staining with a mouse IgG2b (isotype control). (B & C) Comparison of UIC2 (B) or 5D3 (C) shift produced by volasertib and other know ABCB1/ABCG2 inhibitors/substrates, respectively. Known ABCB1 inhibitors: PSC833 (1 μM) and crizotinib (10 μM); known ABCB1 substrate: quinine (50 μM); reported non-ABCB1 substrate: cisplatin (50 μM). Known ABCG2 inhibitors: Ko143 (200 nM) and axitinib (5 μM); known ABCG2 substrate: quercetin (25 μM); reported non-ABCG2 substrate: cisplatin (50 μM). The various tested compounds were present during the 45-min antibody incubation with cells. Fluorescence values are shown as the percentage of maximum labeling obtained in SW620 Ad300 cells incubated with 1 μM PSC833 (UIC2 shift; set as 100%) or 200 nM Ko143 (5D3 shift, set as 100%) and labeled with the respective UIC2 or 5D3 antibody. Mean and SD of the mean channel numbers from histograms obtained from three independent experiments are plotted. * p < 0.05, versus the untreated cells (native staining), respectively.

To et al.Journal of Cancer Therapeutics and Research  2013 2:13DOI : 10.7243/2049-7962-2-13