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Oridonin inhibits 4T1 tumor growth by suppressing Treg differentiation via TGF-β receptor

Jufeng Guo1, Tao Chen2, Zeyu Ma3

  • 1Department of Breast Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, China.

International Immunopharmacology
|August 28, 2020
PubMed

Insights

Oridonin, a Chinese herbal medicine, suppresses triple-negative breast cancer (TNBC) by reducing regulatory T cells (Tregs). This modulation enhances anti-tumor immunity, offering new therapeutic strategies for TNBC.

Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Oridonin, a Chinese herbal medicine, exhibits anti-inflammatory and antitumor properties, notably suppressing breast cancer growth.
  • The precise mechanisms by which oridonin exerts its anti-cancer effects, particularly in triple-negative breast cancer (TNBC), remain incompletely understood.

Purpose of the Study:

  • To elucidate the underlying mechanisms of oridonin's anti-TNBC activity.
  • To investigate the impact of oridonin on regulatory T cells (Tregs) and their function in the tumor microenvironment.

Main Methods:

  • In vitro and in vivo experiments were conducted to assess oridonin's effects on Treg differentiation and function.
  • TGF-β receptor expression levels were analyzed to understand oridonin's mechanism of action.
  • Tumor progression in a 4T1 breast cancer model was monitored.
  • The combination therapy of oridonin with anti-PD-1 was evaluated for its impact on anti-tumor immune response and tumor growth.

Main Results:

  • Oridonin treatment decreased Treg differentiation both in vitro and in vivo, dependent on the downregulation of TGF-β receptor expression.
  • Oridonin attenuated the immunosuppressive capacity of Tregs, which partially affected CD8+ T cell proliferation in vitro.
  • Oridonin significantly delayed the progression of 4T1 tumors in vivo.
  • Combination therapy with oridonin and anti-PD-1 elicited a potent anti-tumor immune response and suppressed 4T1 tumor growth.

Conclusions:

  • Oridonin inhibits TNBC growth by modulating Treg differentiation and function.
  • The findings suggest that oridonin's mechanism involves the downregulation of TGF-β receptor signaling, impacting Treg-mediated immunosuppression.
  • Oridonin, particularly in combination with anti-PD-1, presents a promising therapeutic strategy for TNBC by enhancing anti-tumor immunity.
Keywords:
OridoninPD-1TGF-β receptorTregTriple-negative breast cancer

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