Combining ellagic acid with bevacizumab mediates the cadherin switch and angiogenesis in a glioblastoma model
Analytical and Quantitative Cytopathology and Histopathology, cilt.41, sa.3, ss.75-82, 2019 (Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 41 Sayı: 3
- Basım Tarihi: 2019
- Dergi Adı: Analytical and Quantitative Cytopathology and Histopathology
- Derginin Tarandığı İndeksler: Scopus
- Sayfa Sayıları: ss.75-82
- Anahtar Kelimeler: bevacizumab, cadherins, ellagic acid, glioblastoma, glioma, VEGF, vascular endothelial growth factor
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
OBJECTIVE: To observe the combining effect of ellagic acid (EA) with bevacizumab (BEV) on cadherin switch and angiogenesis of C6-glioma cell line. STUDY DESIGN: Rat C6 glioma cells were treated with EA at 100 µM concentration in combination with BEV at 100 ng/mL concentration for 24, 48, and 72 hours. Cell proliferation was detected by 5-bromo-2'-deoxyuridine (Br-dU) immunocytochemistry. Expression profiles for E-cadherin, N-cadherin, and vascular endothelial growth factor (VEGF) proteins were determined by real-time quantitative PCR (qPCR) and their protein levels by immunocytochemistry, subsequent to EA treatment combined with or without BEV. RESULTS: EA in combination with BEV conspicuously reduced the cell viability of C6-glioma cells for all incubation times. EA upregulated the expression of E-cadherin both at gene and protein levels in a time-independent manner (p<0.001), regardless of the presence of BEV. Conversely, EA with and without BEV reduced N-cadherin expression and immunoreactivity at 48 and 72 hours (p<0.001). EA combined with BEV treatment downregulated the expression of angiogenic protein of VEGF (p<0.001), as well as reduced its immunoreactivity only at 72 hours (p<0.01). CONCLUSION: The present study suggests a successful therapeutic efficacy of EA in combination with BEV, probably through inhibition of the cadherin switch and VEGF expression. EA may be an alternative treatment of drug-resistant gliomas, in combination with BEV.