Figure 3. The inhibitory effects of pharmacological inhibition of USP8 in HCC in vitro. (A) USP8 inhibitor (USP8i) at 0.5, 1 and 2 μmol/L significantly inhibits growth (A) and induces apoptosis (B) in HCC cells. Combination of USP8i with doxorubicin or sorafenib further significantly inhibits further proliferation (C) and induces more apoptosis (D) in HCC cells than single drug alone. USP8i inhibits proliferation (E) and induces apoptosis (F) in HuH6-r and HepG2-r cells. Doxorubicin at 0.1 μM and sorafenib at 0.5 μM were used. Doxorubicin and sorafenib were used in Combi1 and Combi2, respectively. Cell proliferation and apoptosis were determined after 3 days treatment. *p<0.01, compared to control. #p<0.01, compared to doxorubicin or sorafenib alone.