G6PD enables TNBC cells to maintain a relatively high intracellular GSH level during DOX treatment. (A) Intracellular DOX concentration of 231-C3 and 231-M1 cells upon 5 µM DOX treatment for 0, 1, 3, 6, 10, and 24 h respectively. The intracellular level of DOX was normalized to the amount of proteins of the cells. (B) Relative reduced intracellular GSH level of 231-C3 and 231-M1 cells upon 5 µM DOX treatment at 0, 5, 10, 24, and 48 h respectively. GSH levels were normalized to 231-C3 level at 0 h of DOX treatment. (C) 231-C3 cells were transfected with either negative or G6PD-specific siRNA before DOX treatment. GSH levels of 231-C3 cells upon 5 µM DOX treatment at 0, 12, and 24 h respectively were measured and normalized to GSH level at 0 h of DOX treatment. (D) Relative GSH level inside 231-M1 cells upon 5 µM DOX treatment at 0, 12, and 24 h respectively after 231-M1 cells were transfected with either negative or G6PD specific siRNA. GSH levels were normalized to GSH level at 0 h of DOX treatment. (E) Schematic showing the role of G6PD in pentose phosphate pathway to produce NADPH, GSH and the mechanism of high level of G6PD in conferring DOX resistance in TNBC cells.