HCC xenograft model

All animal handling procedures were conducted in accordance with animal care guidelines provided by the Southern Medical University (Shenzhen, China). Male SCID mice at 4-6-weeks-old were obtained from Hunan SJA Laboratory Animal Co., Ltd and housed in a pathogen-free environment with 12-hour light/dark cycles. To generate doxorubicin -sensitive and -resistant HCC cell models, ten million HepG2 and HepG2-r cells in 100 μl of PBS were implanted subcutaneously in the hind flank of each mouse. After developing palpable tumors, the mice were randomly grouped for drug treatment. The specific drug dose and administration routes were indicated in figure legends. Tumor length and width were measured every 5 days, and associated tumor volumes were determined using a standard formula.