Anti-oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient-derived tumor xenograft model

Head Neck. 2019 May;41(5):1260-1269. doi: 10.1002/hed.25554. Epub 2018 Dec 10.

Abstract

Background: Aberrant expression of decoy receptor 3 (DcR3) is considered to be a diagnostic and therapeutic target for human cancers. The aim of this study was to assess DcR3 as a target of the anticancer effects of triptolide (TPL) in preclinical patient-derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC).

Methods: The expression of DcR3 was evaluated through immunohistochemistry, and correlations were examined using clinical variables. The effects of TPL on the expression of DcR3 and cell proliferation were investigated in OSCC cell lines and in PDTX models.

Results: DcR3 overexpression was associated with overall survival and tumor size. TPL significantly decreased tumor growth. Moreover, TPL inhibited the expression of metastasis-associated protein 1 (MTA1), a transcription factor for DcR3 in vivo, in vitro, and in PDTX models.

Conclusion: TPL appeared to exert anticancer effects by repressing DcR3 and MTA1 in vitro, in vivo, and in PDTX models.

Keywords: decoy receptor 3 (DcR3); metastasis-associated protein 1 (MTA1); oral squamous cell carcinoma (OSCC); patient-derived tumor xenograft (PDTX); triptolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Down-Regulation
  • Epoxy Compounds / pharmacology
  • Epoxy Compounds / therapeutic use
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred NOD
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Phenanthrenes / pharmacology*
  • Phenanthrenes / therapeutic use
  • Receptors, Tumor Necrosis Factor, Member 6b / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Receptors, Tumor Necrosis Factor, Member 6b
  • triptolide