Fatty acid synthase as a potential therapeutic target in feline oral squamous cell carcinoma
| Autor: | M. G. O'Sullivan, A. Arora, Jhuma Saha, Erin B. Dickerson, Ali Khammanivong, Jillian Zientek Walz |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Immunoblotting Cat Diseases Real-Time Polymerase Chain Reaction Metastasis 03 medical and health sciences Lactones 0302 clinical medicine Cell Line Tumor medicine Animals Humans Viability assay Orlistat General Veterinary biology Cancer medicine.disease Feline Oral Squamous Cell Carcinoma stomatognathic diseases Fatty acid synthase 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Lipogenesis Immunology Cancer research biology.protein Carcinoma Squamous Cell Cats Immunohistochemistry Mouth Neoplasms Fatty Acid Synthases |
| Zdroj: | Veterinary and comparative oncology. 16(1) |
| ISSN: | 1476-5829 |
| Popis: | Oral squamous cell carcinoma (OSCC) is an aggressive and treatment-resistant malignancy in both feline and human patients. Recent work has demonstrated aberrant expression of fatty acid synthase (FASN) and an increased capacity for lipogenesis in human OSCC and other cancers. In human OSCC, inhibition of FASN decreased cell viability and growth in vitro, and diminished tumour growth and metastasis in murine preclinical models. This study aimed to characterize FASN as a therapeutic target in feline OSCC. Immunohistochemistry revealed high FASN expression in primary feline OSCC tumours, and FASN expression was detected in OSCC cell lines (3 feline and 3 human) by immunoblotting and quantitative real-time-polymerase chain reaction (qRT-PCR). Orlistat, a FASN inhibitor, substantially reduced cell viability in both feline and human OSCC lines, although feline cell lines consistently displayed higher sensitivity to the drug. FASN mRNA expression among cell lines mirrored sensitivity to orlistat, with feline cell lines expressing higher levels of FASN. Consistent with this observation, diminished sensitivity to orlistat treatment and decreased FASN mRNA expression were observed in feline OSCC cells following incubation under hypoxic conditions. Treatment with orlistat did not potentiate sensitivity to carboplatin in the cell lines investigated; instead, combinations of the 2 drugs resulted in additive to antagonistic effects. Our results suggest that FASN inhibition is a viable therapeutic target for feline OSCC. Furthermore, cats may serve as a spontaneous large animal model for human oral cancer, although differences in the regulation of lipogenesis between these 2 species require further investigation. |
| Databáze: | OpenAIRE |
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