(A) FLLL32 and HJC0123 treatment inhibited STAT3 expression and STAT3 phosphorylation HJC0123; protein expression was measured by Western immunoblotting. (B) HJC0123 treatment (1 μM) significantly decreased the expression of pSTAT3(Y705) as early as 2 hours and remained downregulated up to 48 hours; expression was measured by Western immunoblotting. Levels of non-phosphorylated STAT3 were not significantly altered after HJC0123 treatment. (C) HJC0123 (1 μM for 24 hours) significantly reduced nuclear translocation of pSTAT3(Y705), assessed by nuclear fractionation and Western blotting. (D) HJC0123 treatment for 8 hours significantly decreased the transcriptional activity of STAT3 in a dose-dependent manner, measured by Luciferase reporter gene activity assay. (E) LX-2 cells were treated with HJC0123 for 24 hours, Western blotting analysis demonstrated a significant reduction in the expression levels of the STAT3-regulated proteins c-myc, Bcl-2 and SOCS3 in a dose-dependent fashion; HJC0123 did not alter the expression of Cyclin D1. (F) LX- cells were treated with HJC0123, proteins expression measured via Western blotting, expression of JNK and p-JNK did not change significantly after 24 hours treatment (left). TGF-β stimulation (2 ng/mL) did not affect the expression of Smad2/3 but induced Smad2/3 phosphorylation. HJC0123 1 hour pre-treatment with HJC0123 (1 μM) followed by TGF-β stimulation for 8 hours significantly downregulated TGF- β-induced Smad2/3 phosphorylation (right). Experiments were repeated three times and representative results are shown. Error bars indicate ± SE.