1. Academic Validation
  2. Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma

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

  • Life Sci. 2021 Aug 15;279:119359. doi: 10.1016/j.lfs.2021.119359.
Lei Guo 1 Hongbo Li 2 Tianli Fan 1 Yanli Ma 3 Lili Wang 4
Affiliations

Affiliations

  • 1 Department of Infection, Qingdao No. 6 People's Hospital, Qingdao 266033, PR China.
  • 2 Department of Dermatology, Qingdao No. 6 People's Hospital, Qingdao 266033, PR China.
  • 3 Department of Infection, Qingdao No. 6 People's Hospital, Qingdao 266033, PR China. Electronic address: mayanlidoc@126.com.
  • 4 Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao 266033, PR China. Electronic address: qd6hmyl@126.com.
Abstract

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-β1) on lymphocyte activation and the interaction between E1A binding protein P300 (P300), histone acetylation, TGF-β1, 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 down-regulate TGF-β1 expression. Functionally, curcumin inhibited Thrombin to reduce P300-induced histone acetylation in the TGF-β1 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.

Keywords

Anti-programmed cell death-1; Curcumin; E1A binding protein P300; Hepatocellular carcinoma; Immune evasion; Transforming growth factor beta 1.

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