Therapeutic Efficacy of VEGFR and EGFR Inhibitor Combined with Radiotherapy for Squamous Cell Carcinoma in Nude Mice

Objective To evaluate the antitumor efficacy of a combination of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinase activity inhibitor—ZD6474 and radiotherapy for human tumor xenograft model (FaDu，squamous cell carcinoma) and to investigate whether the effects of the treatments were related to changes in tumor microvessel density，proliferation and apoptosis. Methods Tumor-bearing nude mice received either vehicle or ZD6474 with or without irradiation (4 treatment-groups:control;ZD6474 alone;radiotherapy (RT) alone;ZD6474 + RT).The antitumor efficacy of the different treatment modalities was evaluated by the tumor sizes.For the different treatment-groups the tumor vascularisation was evaluated by immunofluorescence analysis of CD34 positive vessel segments (tumor vascular density) and the proliferative capacity and apoptotic degree of the tumor tissue were analysed by the quantification of Ki67 positive nuclei and capase-3 positive cell. Results The tumor growth delay induced by the combined treatment (ZD6474 + RT) was more significant than that induced by ZD6474 or radiotherapy alone.ZD6474 clearly reduced neoangiogenesis.Moreover，proliferative and apoptosis of the tumor tissue was significantly decreased and increased,respectively by ZD6474(P<0.05). Conclusion When irradiation combined with VEGFR and EGFR blockade，significant enhancement of antiangiogenic，antivascular，and antitumor effects were observed.These data provided supports for clinical trials of biologically targeted and conventional therapies in the treatment of cancer.