Decreased VEGF and Cyclin D1 Genes Expression Enhances Chemosensitivity of Human Squamous Cell Carcinoma Cells to 5-Fluorouracil and/or Mesenchymal Stem Cells-Derived Microvesicles

Document Type : Original Article

Authors

1 Lecturer of Oral Pathology, Department of Oral Pathology, Faculty of Dentistry, Suez Canal University, Ismalia, Egypt

2 Assitant professor of oral biology, Department of Oral Biology, Faculty of Dentistry, Cairo University

3 Professor of Medical Biochemistry and Molecular Biology, Department of Medical Biochemistry and molecular biology, Faculty of medicine, Cairo University

Abstract

Background: Among the most common oral cancers is oral squamous cell carcinoma which has high rates of mortality. 5-flurouracil (5-FU) is a widely used chemotherapeutic agent for treatment of head and neck cancers. However, its use has many limitations due to its well- known side effects. Thus, in the current study we aimed to investigate the chemosensitivity of squamous cell carcinoma cells to 5-FU and/or mesenchymal stem cells-derived microvesicles via H&E histopathological examination, in addition to detection of vascular endothelial growth factor (VEGF) and cyclin D1 (CD1) genes’ expression through quantitative RT-PCR analysis.
Material & Methods: Human squamous cell carcinoma cell line (SCC152) was treated by 5-FU or Microvesicles or their combination for 24 and 48 hours. Histopathological examination through H&E stain as well as quantitative RT-PCR analysis, for gene expression of VEGF and CD1, were performed. Finally, statistical analysis of the obtained data and correlation between VEGF and CD1 genes’ expression among different groups were performed.
Results: Regarding the histopathological results, the combination group, as compared to 5-FU or microvesicles treated groups, showed the most obvious improvement where numerous apoptotic bodies were observed at 24hrs, being markedly increased at 48hrs of culture, while viable cells were rarely seen. Concerning the qRT-PCR results, the combination group showed significant decrease in genes’ expression of both VEGF and CD1 than the 5-FU or microvesicles treated groups. Furthermore, correlation between VEGF and CD1 genes’ expression revealed a very good positive correlation.
Conclusions: it was concluded that the combined use of microvesicles and 5-FU resulted in enhanced chemosensitivity of squamous cell carcinoma cells more than the use of either 5-FU or microvesicle alone. In addition, down regulation of VEGF gene expression was associated with decreased CD1 gene expression.

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