Abstract:Objective The nerve growth factor receptor (TrkA) gene is an independent marker of the favourable prognosis of neuroblastoma (NB). High expression of TrkA can not only induce differentiation and inhitit proliferation of NB cells but can also be involved in the regulation of tumor angiogenesis. This study aims to investigate the role of the TrkA gene in human NB angiogenesis. Methods The NB SY5Y cells were named SY5Y TrkA cells and SY5Y Vec cells after being transfected with TrkA gene and PBPSTR1 empty vector respectively, and the NB SY5Y cells without transfection were named the SY5Y cells. Fifteen nude mice were assigned into a Control group, an Empty Vec group an Experiment group (n=5 each). The SY5Y cells of the Control group, the SY5Y Vec cells of the Empty Vec group and the SY5Y TrkA cells of the Experiment group were inoculated. The mice were then sacrificed 50 days after inoculation. The tumor volume was measured; the microvessel density (MVD) of the tumor was evaluated and the expression of vascular endothelial growth factor (VEGF) was determined by RT PCR and immunohistochemistry. Results The tumor volume in the Experiment group ( 0.39 ± 0.02 cm 3 ) was significantly smaller than that of the Control group ( 1.74 ± 0.49 cm 3 ) and also was smaller than the Empty Vec group ( 1.80 ± 0.75 cm 3 ) (P< 0.01 ). The expressions of VEGF mRNA and VEGF protein in the Experiment group were significantly lower than those of both the Control and the Empty Vec groups (P< 0.01 ). The MVD in the Experiment group ( 4.08 ± 4.72% ) was also significantly lower than that of the Control ( 27.21 ± 14.58% ) and Empty Vec groups ( 27.76 ± 14.15% ) (P< 0.01 ). Conclusions Angiogenesis and tumor growth of human NB can be effectively inhibited by the TrkA gene. This experiment provides a theoretical basis for the treatment of NB with anti angiogenesis gene therapy.
