Fig. 1

Hypoxia-induced sorafenib resistance in HCC cells is dependent on hyperactived mitophagy. a Schematic diagram showing establishment of sorafenib resistant (SR) and hypoxia-induced sorafenib resistant (H-SR) cells. b, c Evaluation of the half inhibitory concentration (IC50) of sorafenib in the indicated groups. d Transmission electron micrographs showing mitophagy in the indicated cells. e Immunoblots showing expression levels of the indicated proteins in control and Huh7-H-SR cells treated with/out chloroquine (CLQ). f Immunoblot showing expression levels of indicated proteins in control, hypoxia, SR and Huh7-H-SR cells. g, h Correlation between PINK1 expression and ABCB1 (g) and ABCG2 (h) in HCC patients from TCGA database. i Number of colonies formed by Huh7, Huh7-H-SR and Huh7-H-SR cells with 3MA (dosage: 5 mM) under sorafenib treatment (dosage: 5.13 μM). j Cell viability of Huh7, Huh7-H-SR and Huh7-H-SR cultured with 3MA under sorafenib treatment for varying durations. k Number of colonies formed by Huh7, Huh7-H-SR and Huh7-H-SR transfected with shPINK1 under sorafenib treatment. l Percentage of viable Huh7, Huh7-H-SR and Huh7-H-SR transfected with shPINK1 under sorafenib treatment for varying durations. Data are shown as mean ± SEM from three independent experiments, **p < 0.01, ***p < 0.001