Fig. 3: ATP regulates HIF-1α signaling via PI3K/AKT pathway and P2Y2 receptor.
From: Extracellular ATP promotes breast cancer chemoresistance via HIF-1α signaling
A Western blotting illustrated that ATP-driven HIF-1α and HIF-1α target proteins were attenuated by LY294002 (PI3K/AKT inhibitor). B–D MDA-MB-231 and MCF-7 cells were treated with/without cisplatin plus S3I-201 or LY294002 for 2 days (B, C) or 3 weeks (D). Cell counting via trypan blue dye exclusion assay (B), Annexin V/PI dual staining assay (C), and clonogenic assay (D) showed that ATP-driven cisplatin resistance was attenuated by S3I-201 or LY294002. E, F MDA-MB-231 and MCF-7 cells were transfected with NC-siRNA or ADM-siRNA or PDK1-siRNA for 48 h, followed by cisplatin treatment alone or in combination with ATP for a further 2 days. Cell counting via trypan blue dye exclusion assay (E) and Annexin V/PI dual staining assay (F) showed that ATP-driven cisplatin resistance was attenuated by ADM-siRNA or PDK1-siRNA. G Western blotting proved that P2Y2-siRNA attenuated ATP-driven expression alterations in HIF-1α signaling. Data are representative of at least three independent experiments. Error bars represent means ± SD from triplicate experiments. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant.
