Experimental Research on the TrkA Gene Inhibition of Angiogenesis in Human Neuroblastoma

OBJECTIVE This study was designed to investigate the feasibility of gene therapy for human neuroblastoma (NB) with the TrkA gene inhibition of tumor angiogenesis, growth and metastasis.

METHODS Three groups of cells including SY5Y, SY5Y-TrkA and SY5Y-Vec NB cells, were cultured by routine methods. Comparison of oncogenicity was performed among the three groups of cells. Tumor volume and angiogenesis in nude mice were also compared with VEGFmRNA expression (by RT-PCR analysis), immunohistochemistry and microvessel counting.

RESULTS The TrkA-transfected SY5Y NB cells showed significantly reduced oncogenicity and tumor angiogenesis. Tumor volumes were statistically different among the control, Empty-Vec and the experimental group, namely 1.736±0.485cm³, 1.803±0.751cm³ and 0.395±0.015cm³, respectively (P< 0.01). The difference of vascular endothelial growth factor (VEGF) expression between the experimental group and the control group was significant (P<0.01). Microvessel density (MVD) of the control, Empty-Vec and the experimental group were 27.21 ±14.58, 27.76±14.15 and 4.08±4.72 respectively, with statistical differences from the experimental group (P< 0.001).

CONCLUSION The tumor angiogenesis and growth of NB were significantly inhibited by the TrkA gene. These studies provide a theoretical basis for application of NB antiangiogenesis gene therapy.