Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells.
Bottom Line: Our preliminary data show small interfering RNA-mediated silence of APE1 experiments, which further supports this hypothesis.APE1-small interfering RNA significantly inhibited tumor angiogenesis by downregulating in vitro expression of FGF2 and FGFR3 in human umbilical vein endothelial cells in Matrigel tube formation assay, and further inhibited tumor growth in vivo in a mouse xenograft model.Thus, the proposed APE1-FGF2 and FGFR3 pathway may provide a novel mechanism for regulation of FGF2 and FGFR3 by APE1 in tumor angiogenesis.
Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.Show MeSH
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Mentions: A BALB/c mouse osteosarcoma xenograft model using human osteosarcoma 9901 cells was used to further demonstrate that APE1-siRNA inhibits tumor angiogenesis and growth. These xenografts were treated with APE1-siRNA or PBS for control, by i.t. injection. The growth of tumors treated with APE1-siRNA was slower than that of the control group (P = 0.0068), and the results of xenograft growth are similar with our before data republished in Cancer Science.(25) Tumor sections were analyzed using immunohistochemistry, and representative images are shown in Figure 5. As expected, the expression levels of APE1, FGF2 and FGFR3 were significantly lower in the APE1-siRNA treatment group (67.8%, 66.0% and 59.9%, respectively) compared to the control group (P < 0.0001; Fig. 5a,b). The density of CD34-positive vessels when using anti-CD34 antibody in tumor sections was much lower in tumors with APE1-siRNA than in the control (P < 0.0001; Fig. 5a,c). These results correlate well with tumor growth and lower expression of APE1, FGF2 and FGFR3 in Figure 5(a,b) (less FGF2 and FGFR3 downregulated by APE1-siRNA, and less tumor angiogenesis and growth). Taken together, these results suggest that APE1-siRNA significantly inhibits tumor angiogenesis and growth in vivo by downregulating FGF2 and FGFR3 expression.
Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.