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: To explore the biological significance of the silencing of APE1 upregulated FGF2 and FGFR3 expression in tumor angiogenesis, transwell migration assays were carried out in HUVEC. As shown in Figure 4(a,b), a smaller number of HUVEC was migrated in the 0.3 nM APE1-siRNA treatment group than in the control group (36.20 ± 4.76 vs 113.20 ± 4.97, P < 0.0001) and, unexpectedly, this reduced migration activity was largely restored by an addition of recombinant FGF2 (58.80 ± 8.35 vs 36.20 ± 4.76, P = 0.0008). Furthermore, Matrigel tube formation assays carried out in HUVEC using TCM showed formation of fewer capillary tubes in the presence of TCM derived from cells with APE1-siRNA (0.3 nM) in a dose-dependent manner as compared to the control group (1.80 ± 0.84 vs 28.00 ± 5.83, P < 0.0001; Fig. 4c,d). Similarly, this reduced angiogenic capacity of the TCM was mostly restored with an addition of recombinant FGF2 (8.60 ± 2.70 vs 1.80 ± 0.84, P = 0.0007; Fig. 4c,d).
Affiliation: Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.