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

雷公藤内酯醇通过下调DcR3在体外、体内和临床前患者来源肿瘤异种移植模型中发挥抗口腔癌作用

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作者:Cheng-Yu Yang ,Chih-Kung Lin ,Cheng-Chih Hsieh ,Chang-Huei Tsao ,Chun-Shu Lin ,Bo Peng ,Yen-Tzu Chen ,Chun-Chieh Ting ,Wei-Chin Chang ,Gu-Jiun Lin ,Huey-Kang Sytwu ,Yuan-Wu Chen

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.

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