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. 2020 Jan 13;12(1):195. doi: 10.3390/cancers12010195

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Sitravatinib restores apoptosis sensitivity in multidrug-resistant cancer cells overexpressing ABCB1 or ABCG2. Dot plots (upper panel) and quantification (lower panel) of (a) drug-sensitive parental KB-3-1 and the ABCB1-overexpressing subline KB-V-1treated with either DMSO (control), 5 μM of sitravatinib (+sitravatinib), 500 nM of colchicine (+colchicine) or a combination of 500 nM of colchicine and 5 μM of sitravatinib (+colchicine +sitravatinib) and (b) drug-sensitive parental S1 and the ABCG2-overexpressing subline S1-M1-80 treated with either DMSO (control), 5 μM of sitravatinib (+sitravatinib), 5 μM of topotecan (+topotecan) or a combination of 5 μM of topotecan and 5 μM of sitravatinib (+topotecan + sitravatinib). Cells were treated with respective regimens, isolated and analysed by flow cytometry as described previously [44]. Representative dot plots and quantifications of apoptotic cell populations are presented as mean ± SD calculated from at least three independent experiments are shown. *** p < 0.001, versus the same treatment in the absence of sitravatinib.

Sitravatinib restores apoptosis sensitivity in multidrug-resistant cancer cells overexpressing ABCB1 or ABCG2. Dot plots (upper panel) and quantification (lower panel) of (a) drug-sensitive parental KB-3-1 and the ABCB1-overexpressing subline KB-V-1treated with either DMSO (control), 5 μM of sitravatinib (+sitravatinib), 500 nM of colchicine (+colchicine) or a combination of 500 nM of colchicine and 5 μM of sitravatinib (+colchicine +sitravatinib) and (b) drug-sensitive parental S1 and the ABCG2-overexpressing subline S1-M1-80 treated with either DMSO (control), 5 μM of sitravatinib (+sitravatinib), 5 μM of topotecan (+topotecan) or a combination of 5 μM of topotecan and 5 μM of sitravatinib (+topotecan + sitravatinib). Cells were treated with respective regimens, isolated and analysed by flow cytometry as described previously [44]. Representative dot plots and quantifications of apoptotic cell populations are presented as mean ± SD calculated from at least three independent experiments are shown. *** p < 0.001, versus the same treatment in the absence of sitravatinib.