Recombinant adenovirus APE1 siRNA enhances efficacy of bevacizumab on implanted osteosarcoma.

Objective:To investigate the effect of APE1-targeting siRNA(APE1 siRNA) on implanted osteosarcoma and its synergetic role with bevacizumab(vascular endothelial growth factor antibody,Avastin).Methods: Human osteosarcoma 9901 cell-bearing nude mouse model was established.Sixteen tumor-bearing mice were randomly divided into 4 groups: EGFP control group,APE1 siRNA group,Avastin group and combined treatment group(Avastin+APE1 siRNA).The growth of implanted tumors was measured during treatment,and tumor inhibitotry rate was calculated.Meanwhile,microvessel density(MVD) and Ki67 expression in tumor tissues were examined by immunohistochemistry.Apoptosis of tumor cells was examined by TUNEL.Hypoxia status of tumor tissues was determined by laser cofocal scanning microscopy.Expression of VEGF protein in tumor tissues was detected by Western blotting.Results: The tumor inhibitory rate of Avastin+APE1 siRNA group was significantly increased compared with those of APE1 siRNA group and Avastin group(P0.01).The MVD and Ki67 expressions in therapy groups were significantly lower than those in control group;moreover,the MVD and Ki67 expressions in Avastin+APE1 siRNA group were remarkedly lower than those in APE1 siRNA group or Avastin group(P0.01).The apoptosis index(AI) in therapy groups was significantly higher than that in control group,with AI in Avastin+APE1 siRNA group being markedly higher than those in the other two groups(P0.01).Hypoxia status in tumor tissues was enhanced and VEGF expression was inhibited in APE1 siRNA group or Avastin group;furthermore,hypoxia status and VEGF expression in Avastin+APE1 siRNA group were greatly changed.Conclusion: APE1-targeting siRNA can inhibit the angiogenesis and growth of implanted osterosarcoma,and induce apoptosis of tumor cells,which shows a synergistic role with Avastin in the treatment of osteosarcoma.