TrkA基因的表达抑制神经母细胞瘤血管生成的实验研究

张继红; 张锦华; 刘戈飞

TrkA基因的表达抑制神经母细胞瘤血管生成的实验研究

Experimental Research of TrkA Gene Inhibiting Angiogenesis of Human Neuroblastoma

摘要

摘要: 目的:探讨TrkA基因通过抑制神经母细胞瘤(NB)血管生成而阻止其生长、转移的可行性。方法:常规培养对照组SY5Y细胞、TrkA基因高表达的实验组细胞(SY5Y-TrkA)和表达载体基因的空载体组细胞(SY5Y-Vec);比较三组细胞的裸鼠皮下致瘤性;通过RT-PCR、免疫组织化学、微血管面积计算检测并比较三种细胞所致的肿瘤瘤体内血管生成情况。结果:SY5Y-TrkA细胞在裸鼠皮下的致瘤性和其所致肿瘤的血管生成能力明显下降。肿瘤终体积:对照组1.736±0.485cm³,空载体组1.803±0.751cm³,实验组0.3945±0.015cm3(P<0.01);对照组与实验组相比,血管内皮生长因子(VEGF)的表达差别显著(P<0.01);微血管密度(MVD):对照组27.21±14.58,空载体组27.76±14.15,实验组4.08±4.72(P<0.01)。结论:TrkA基因能有效抑制神经母细胞瘤的血管生成和肿瘤生长,为应用基因抗血管治疗神经母细胞瘤提供理论依据。

Abstract: Objective : To investigate the feasibility of gene therapy for human neuroblastoma withTrkA gene inhibiting angionenesis. Methods : We cultured regularly the three groups of cells: SYSYand SYSY-TrkA and SYSY-Vec NB cells. The tumorigenesis of the three groups of cells was tom-pared. The tumor volume and angiogenesis of tumors in nude mites was compare and analysed by RT-PCR and immunohistochemistry and microvessel counting. Results : The capability of tumorigenesis andangiogenesis of the TrkA-SYSY cells in nude mites was greatly reduced. Tumor volume: Control group1.736 (0.485cm3,Empty-Vet group 1.803 (0.751cm³,Experiment group 0.3945 (0.015cm³ ( p (0.01);Thedistinction of vascular endothelial growth factor (VEGF)expression between experiment group and con-trol group is significant (p (0.01); Microvessel density ( MVD):Control group 27.21(14.58 , Empty -Vecgroup 27.76 (14.15(,Experiment group 4.08 (4.72 ((p (0.01). Conclusion : The angiogenesis and tumorgrowth of human neuroblastoma can be effectively inhibited by TrkA gene. This experiment provides atheoretical basis for neuroblastoma angiostatic gene therapy.

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