2. Academic Validation
  3. Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model

Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model

  • Arch Oral Biol. 2024 Oct:166:106043. doi: 10.1016/j.archoralbio.2024.106043.
Yanlin Wu 1,  Guilian Zhang 2,  Panpan Yin 1,  Jinlin Wen 1,  Ying Su 1,  Xinyan Zhang 3
Affiliations

Affiliations

  • 1 Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, No.4 Tiantanxili, Dongcheng District, Beijing 100050, China.
  • 2 Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, No.4 Tiantanxili, Dongcheng District, Beijing 100050, China; Department of Stomatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
  • 3 Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, No.4 Tiantanxili, Dongcheng District, Beijing 100050, China. Electronic address: xinyanzhangzh@126.com.
PMID: 38968906 DOI: 10.1016/j.archoralbio.2024.106043
Abstract

Objective: Combing PD-1/PD-L1 Immune Checkpoint inhibitors with Natural Products has exhibited better efficacy than monotherapy. Hence, the purpose of this research was to examine the anti-cancer effects of brusatol, a natural quassinoid-terpenoid derived from Brucea javanica, when used in conjunction with an anti-mouse-PD-1 antibody in a murine head and neck squamous cell carcinoma (HNSCC) model and elucidate underlying mechanisms.

Design: A murine HNSCC model and an SCC-15 cell xenograft nude mouse model were established to investigate the anti-cancer effects of brusatol and anti-PD-1 antibody. Mechanistic studies were performed using immunohistochemistry. Cell proliferation, migration, colony formation, and invasion were evaluated by MTT, migration, colony formation, and transwell invasion assays. PD-L1 levels in oral squamous cell carcinoma (OSCC) cells were assessed through qRT-PCR, flow cytometry, and western blotting assays. The impact of brusatol on Jurkat T cell function was assessed by an OSCC/Jurkat co-culture assay.

Results: Brusatol improved tumor suppression by anti-PD-1 antibody in HNSCC mouse models. Mechanistic studies revealed brusatol inhibited tumor cell growth and angiogenesis, induced Apoptosis, increased T lymphocyte infiltration, and reduced PD-L1 expression in tumors. Furthermore, in vitro assays confirmed brusatol inhibited PD-L1 expression in OSCC cells and suppressed cell migration, colony formation, and invasion. Co-culture assays indicated that brusatol's PD-L1 inhibition enhanced Jurkat T cell-mediated OSCC cell death and reversed the inhibitory effect induced by OSCC cells.

Conclusions: Brusatol improves anti-PD-1 antibody efficacy by targeting PD-L1, suggesting its potential as an Adjuvant in anti-PD-1 immunotherapy.

Keywords

Brusatol; Natural products; Programmed cell death 1 ligand 1; Squamous cell carcinoma of head and neck.

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