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

• Published in: Head & neck Vol. 41; no. 5; pp. 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: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2019; Wiley Subscription Services, Inc
• 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; triptolide; patient-derived tumor xenograft (PDTX); decoy receptor 3 (DcR3); metastasis-associated protein 1 (MTA1); oral squamous cell carcinoma (OSCC)
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.25554

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.