Reem Mebed , Yasser BM Ali, Nahla Shehata, Nahla Gamal, Nadia El-Guendy, Abdel-Rahman Zekri and Salwa Sabet* Pages 374 - 383 ( 10 )
<p>Background: Bevacizumab (Bev) resistance is hypothesized to be overcome by combining inhibitors of other signalling pathways. <p> Objective: We aimed to study the effect of combining Bev with knocked down β-catenin (Bev-β-cat-siRNA) on the expression of VEGF-A, Slug, NFκB, and its two target genes, c-Flip and FasR, in HepG2. Expression of VEGF-A and Slug was also studied in Caco-2 cells. <p> Methods: Cultured cells were divided into six groups 1) cells treated with Bev, 2) cells treated with β-catenin-siRNA, 3) cells treated with Bev-β-cat-siRNA, 4) cells treated with negative control, 5) cells treated with Bev-negative control, and 6) untreated cells. Expressions were assessed using qPCR and western blotting. <p> Results: Bev-β-cat-siRNA significantly reduced the mRNA level of VEGF-A, which was initially increased in response to Bev alone in HepG2 but not in Caco-2. Additionally, Bev-β-cat-siRNA significantly decreased Slug mRNA level compared to Bev treated HepG2 cells. In contrast, VEGF-A and Slug mRNA levels in Bev group were remarkably lower than Bev-β-cat-siRNA in Caco-2 cells. Distinct β-catenin and Slug protein expressions were noticed in HepG2 and Caco-2 cells. On the other hand, Bev-β-catsiRNA remarkably reduced the level of NFκB, FasR, and c-Flip compared to Bev treated HepG2 cells, although the difference was not statistically significant. <p> Conclusion: We conclude that combining Bevacizumab with knocked down β-catenin reduces the expression of VEGF-A and Slug in HepG2 but not in Caco-2 cells.</p>
Bevacizumab, β-catenin, VEGF-A, Slug, NFκB, C-Flip, FasR.
Chemical control unit, National Organization for Research and Control of Biologicals, Cairo, Molecular Biology unit, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Lot release unit, National Organization for Research and Control of Biologicals, Cairo, Department of Applied Research, Research & Development Sector, VACSERA, Cairo, Department of Cancer Biology, National Institute of Cancer, Cairo University, Department of Cancer Biology, National Institute of Cancer, Cairo University, Department of Zoology, Faculty of Science, Cairo University