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

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.

SUBMITTER: Yang CY

PROVIDER: S-EPMC6590365 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Yang Cheng-Yu CY Lin Chih-Kung CK Hsieh Cheng-Chih CC Tsao Chang-Huei CH Lin Chun-Shu CS Peng Bo B Chen Yen-Tzu YT Ting Chun-Chieh CC Chang Wei-Chin WC Lin Gu-Jiun GJ Sytwu Huey-Kang HK Chen Yuan-Wu YW

Head & neck 20181210 5

<h4>Background</h4>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).<h4>Methods</h4>The expression of DcR3 was evaluated through immunohistochemistry, and correlations were examined using clinical variables. The effects of TPL o ...[more]

PMID: 30537218

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Project description:Purpose: Authentic preclinical models of renal cell carcinoma (RCC) are lacking. We aimed to establish and characterize primary RCC cultures and demonstrate the feasibility of evaluating drug responses in vitro and in vivo. Materials and Methods: Previously published methodology, with minor modifications, was used to establish, cryopreserve, and serially passage RCC cells from nephrectomy and tumorgraft specimens. Cells were characterized for immuno- and molecular phenotype by immunochemistry, DNA sequencing and gene expression profiling. Tumorigenic potential was evaluated by implanting cells under the renal capsule of immunocompromised mice. The ability to monitor xenograft growth by magnetic resonance imaging (MRI) was investigated. Responses to a tyrosine kinase inhibitor (TKI) and an mTOR inhibitor were measured. Results: Primary cultures were successfully established from 11 clear cell and 1 chromophobe RCC, cryopreserved and serially passaged. Retention of immuno- and molecular phenotypes was demonstrated. Cultured cells formed xenografts in mice that could be measured by MRI. Patient-specific responses to drugs were observed in vitro and response to an TKI was confirmed in vivo. Conclusions: Our study is the first to show the derivation of primary cultures from RCC tumorgrafts, and to demonstrate the ability of primary RCC cultures to generate xenografts in mice. Our results suggest the feasibility of establishing large, well-annotated banks of RCC primary cultures for high-throughput drug screening in vitro and validation in vivo, providing a versatile platform together with xenografts and patient-derived precision-cut tissue slice tumorgrafts we developed previously for precilinical studies of RCC. Microarray analyses were performed to compare the gene expression profile of one of the primary cultures (case 7) to its parental tumor and tissue slice tumorgrafts in the study. Tissue slice grafts and parent tumors were preserved in Allprotect tissue reagent (Qiagen, Valencia, CA) at -20Â°C prior to RNA extraction using an AllPrep DNA/RNA/Protein Mini Kit (Qiagen, Valencia, CA). The quality of RNA was determined using an Agilent 2100 Bioanalyzer (Agilent Biotechnologies, Santa Clara, CA). Microarray hybridization was performed using Illumina Human HT-12 v4 Beadchips (Illumina Inc., San Diego, CA) according to the manufacturerâ??s directions. Expression data was rank invariant normalized using BeadStudio software (Illumina Inc.).

Dataset Information

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

Publications

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

Similar Datasets

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