title: Triptolide downregulates Treg cells and the level of IL-10, TGF-β, and VEGF in melanoma-bearing mice.
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.
authors: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors: Biao
authors: B
authors: Liu
authors: Hongqi
authors: H
authors: Zhang
authors: Jian
authors: J
authors: Li
authors: Cheng
authors: C
authors: Lu
authors: Gao
authors: G
authors: Chen
authors: Ge
authors: G
authors: Zhang
authors: Aiping
authors: A
authors: Lu
authors: Xiaojuan
authors: X
authors: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D029757:Tripterygium / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010616:Phenanthrenes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; C001899:triptolide