Triptolide downregulates Treg cells and the level of IL-10, TGF-β, and VEGF in melanoma-bearing mice

Planta Med. 2013 Oct;79(15):1401-7. doi: 10.1055/s-0033-1350708. Epub 2013 Aug 23.

Abstract

Regulatory T cells play a key role in suppressing tumor immunity. Triptolide, a major active component isolated from the Chinese medicinal herb Tripterygium wilfordii, has been proven to possess multiple antitumor activities. Here, we investigated the effect of triptolide on regulatory T cells and on the level of IL-10, transforming growth factor-β, and vascular endothelial growth factor in tumor-bearing mice. Fifty male C57BL/6 mice were randomly grouped as follows: normal control group, model group with B16-F10 cells implanted, and three treatment groups with cyclophosphamide, triptolide-high dose, triptolide-low dose. The proportion of regulatory T cells in the spleen and axillary lymph nodes was evaluated by flow cytometric analysis. Production of cytokines IL-10, transforming growth factor-β, and vascular endothelial growth factor in serum was measured using enzyme-labeled immunosorbent assay kits. The mRNA levels of Foxp3, IL-10, and transforming growth factor-β in the spleen and vascular endothelial growth factor in tumor tissue were detected by real-time PCR. The results showed that triptolide significantly decreased the proportion of regulatory T cells and lowered the Foxp3 level in the spleen and axillary lymph nodes of tumor-bearing mice. Production of IL-10 and transforming growth factor-β in peripheral blood, and the mRNA level of IL-10 and transforming growth factor-β in the spleen were also decreased. Additionally, triptolide could remarkably inhibit production of vascular endothelial growth factor in tumor-bearing mice. In conclusion, our study demonstrated that triptolide might inhibit tumor growth by inhibiting regulatory T cells and some cytokines such as IL-10 and transforming growth factor-β, as well as production of vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Down-Regulation
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Epoxy Compounds / pharmacology
  • Epoxy Compounds / therapeutic use
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Lymph Nodes / immunology
  • Male
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Mice, Inbred C57BL
  • Phenanthrenes / pharmacology*
  • Phenanthrenes / therapeutic use
  • Phytotherapy
  • RNA, Messenger / metabolism
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / blood
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Tripterygium / chemistry*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Phenanthrenes
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • triptolide