Fig. 5

PI3K signaling pathway activation by rHMGB1. MDA-MB-231 P and MDA-MB-231 BM cells were starved in 0.1% BSA DMEM for 48 h, then treated with 100 ng/ml rHMGB1 or in combination with either 150 nM GDC-0941 or 2 μM AT13148 in 0.1% BSA DMEM for 30 min and 24 h (a and b). Relative protein expression levels are of p-AKT normalized by AKT and PD-L1 normalized by β-actin. Results are presented as mean ± SD of three independent experiments. Data are expressed as mean ± SD of four experiments. *P < 0.05. The schematic diagram illustrates the potential of the RAGE-PI3K/AKT signaling pathway in which HMGB1 regulates breast cancer cell aggressiveness and PD-L1 expression. T cells can use PD-1 to ligate with PD-L1 on cancer cells leading to T cell apoptosis (c). The dark lines represent the data in this study