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

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...

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Bibliographic Details
Published in:Head & neck 2019-05, Vol.41 (5), p.1260-1269
Main Authors: Yang, Cheng‐Yu, Lin, Chih‐Kung, Hsieh, Cheng‐Chih, Tsao, Chang‐Huei, Lin, Chun‐Shu, Peng, Bo, Chen, Yen‐Tzu, Ting, Chun‐Chieh, Chang, Wei‐Chin, Lin, Gu‐Jiun, Sytwu, Huey‐Kang, Chen, Yuan‐Wu
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Alkylating - pharmacology
Antineoplastic Agents, Alkylating - therapeutic use
Biomarkers, Tumor - metabolism
Cancer
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell culture
Cell Proliferation
decoy receptor 3 (DcR3)
Diterpenes - pharmacology
Diterpenes - therapeutic use
Down-Regulation
Epoxy Compounds - pharmacology
Epoxy Compounds - therapeutic use
Head and neck
Heterografts
Humans
Immunohistochemistry
Metastases
metastasis‐associated protein 1 (MTA1)
Mice
Mice, Inbred NOD
Mouth Neoplasms - drug therapy
Mouth Neoplasms - metabolism
Mouth Neoplasms - pathology
Oral cancer
Oral squamous cell carcinoma
oral squamous cell carcinoma (OSCC)
Original
patient‐derived tumor xenograft (PDTX)
Phenanthrenes - pharmacology
Phenanthrenes - therapeutic use
Receptors, Tumor Necrosis Factor, Member 6b - metabolism
Squamous cell carcinoma
Therapeutic applications
Triptolide
Xenograft Model Antitumor Assays
Xenografts
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Summary: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.
ISSN:1043-3074
1097-0347
DOI:10.1002/hed.25554