Fig. 3

ABCG2 inhibition and depletion synergizes with THZ531 in similar fashion as synergistic kinase inhibitors. A Proliferative responses of dose ranges of transcriptional CDK inhibitors THZ531, THZ1, CDKI-73, PHA-767491, SR4835 and flavopiridol in control cells (Hs578T with inducible Cas9 and ABCG2 gRNA, without addition of doxycycline) or ABCG2 knockout cells (with addition of doxycycline). B Proliferative response to THZ531 (0.1 µM), THZ1 (0.0316 µM), CDKI-73 (0.1 µM), PHA-767491 (1 µM) in untransfected (mock) Hs578T cells or Hs578T cells treated with siKP (ctrl) or siABCG2. C Proliferative responses of dose ranges of transcriptional CDK inhibitors THZ531, THZ1, CDKI-73, PHA-767491, SR4835 and flavopiridol, alone, or in combination with KO143 (1 µM) or lapatinib (1 µM). D Effects of combination treatment of KO143 (1 µM) with THZ531 (0.1 µM) on FUCCI cell cycle (upper, 24 h) and cell death AnnexinV/PI (lower, 72 h) in Hs578T cells. E ABC-transporter siRNA screen showing proliferative responses upon knockdown of ABC-transporter genes together with DMSO or THZ531 (0.1 µM) treatment. Means of DMSO or treatment were compared using multiple comparisons (Dunnet’s correction) from two-way ANOVA between siKP and siABCG2. F Proliferative responses of combination treatment of a dose range of either ABCG2 inhibitor KO143 or ABCB1/ABCC1 inhibitor Verapamil with THZ531 0.1 µM. All data are the mean (± SD) from three independent experiments