Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks near the top in the global list of malignancies causing cancer-related death. Recently, combination therapy has gained popularity in treating this cancer. We tried to investigate the efficacy of combined treatment with curcumin and anti-programmed cell death-1 (anti-PD-1) in HCC. Hep3B cells were treated with different concentrations of curcumin, followed by determination of Hep3B cell proliferation and programmed cell death ligand-1 (PD-L1) expression. Then, Hep3B cells were co-cultured with peripheral blood mononuclear cells (PBMCs), after which the Hep3B cell growth and immune activity were detected following treatment with curcumin and/or anti-PD-1. Besides, we investigated the effect of transforming growth factor beta 1 (TGF-beta 1) on lymphocyte activation and the interaction between E1A binding protein P300 (P300), histone acetylation, TGF-beta 1, and thrombin. Additionally, the synergistic role of curcumin and anti-PD-1 in mouse models of HCC was studied. Curcumin retarded Hep3B cell growth and reduced surface PD-L1 expression in Hep3B cells. After co-culture of Hep3B cells and PBMCs, curcumin had a synergistic effect with anti-PD-1 to slow Hep3B cell proliferation, activate lymphocytes, inhibit immune evasion, and downregulate TGF-beta 1 expression. Functionally, curcumin inhibited thrombin to reduce P300-induced histone acetylation in the TGF-beta 1 promoter region, and anti-PD-1 suppressed binding of PD-1 and PD-L1 to promote immune activity; the combination of the two showed better in vitro anti-cancer effects. In vivo, curcumin combined with anti-PD-1 also lowered HCC growth rate and improved the tumor microenvironment. In conclusion, the combination of curcumin and anti-PD-1 is synergistically effective in the treatment of HCC treatment.

Automated summary

The study investigated the efficacy and mechanism of combined treatment with curcumin and anti-PD-1 in HCC, revealing synergistic anti-cancer effects in both in vitro and in vivo models.