title: Expression of angiogenic growth factors VEGF, bFGF and ANG1 in colon cancer after bevacizumab treatment in vitro: A potential self-regulating mechanism.
abstract: The present study aimed to examine changes in the expression of angiogenic growth factors in vascular endothelial cells isolated from colon cancer after bevacizumab treatment in vitro, and to explore a potential mechanism of their self-regulation as a possible mechanism for antiangiogenic therapy failure in clinics. Vascular endothelial cells were isolated from tumors of colon cancer patients and transfected with recombinant adeno-associated virus type 2-vascular endothelial growth factor (VEGF) or pGIPZ-VEGF RNA interference in order to upregulate or downregulate VEGF expression. Changes in VEGF expression and its correlation with the expression of angiogenesis-related factors, including basic fibroblast growth factor (bFGF) and angiopoietin 1 (ANG1), after treatment with bevacizumab in vitro, were investigated. The results showed that in cells with VEGF overexpression, bFGF and ANG1 were downregulated, whereas in cells in which VEGF was knocked down, upregulation of bFGF and ANG1 was detected. In cells treated with bevacizumab, a significant upregulation of VEGF and downregulation of bFGF and ANG1 were observed. Our data indicate that after bevacizumab treatment, a potential self-regulating mechanism of angiogenic growth factors in colon cancer-derived endothelial cells is activated, which may explain why current antiangiogenic therapy with bevacizumab has limited effects in prolonging the survival of colon cancer patients.
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Minjian
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of General Surgery, Central Hospital of Ezhou, Hubei 436000, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D012259:Ribonuclease, Pancreatic / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000068258:Bevacizumab; C046366:angiogenin; D012259:Ribonuclease, Pancreatic