Conclusion
P-T3H2 suppressed HCC progression through the stabilization of HNF4α protein and may be a promising therapeutic candidate for clinical application in the treatment of HCC.
Methods
The expression of TRIB3 and HNF4α was evaluated using western blot and immunohistochemistry (IHC). Hepatic functions and cellular senescence of HCC cells were evaluated through periodic acid-Schiff (PAS) staining, acetylated low-density lipoprotein (ac-LDL) uptake and senescence-associated β-galactosidase (SA-β-gal) activity staining, respectively. RNA-Seq analysis was performed to identify differentially expressed genes in Huh7 cells treated with P-T3H2. The impact of P-T3H2 on HCC malignancy was assessed in vitro and in vivo.
Results
TRIB3 exhibited a negative correlation with HNF4α in both human and mouse HCC tissues. The administration of P-T3H2 significantly inhibited the malignancy of HCC cells. Additionally, P-T3H2 stabilized HNF4α protein and facilitated the restoration of hepatic functions and the cellular senescence in HCC cells. RNA-Seq analysis demonstrated that P-T3H2 enhanced the transcriptional activity of HNF4α in HCC. Furthermore, P-T3H2 effectively suppressed the carcinogenesis and progression of HCC in mice.