A study of angiogenesis in head and neck cancers and its application to cancer gene therapy

将血管内皮细胞生长因子(VEGF)基因导入头颈部癌细胞系，观察基因诱导对肿瘤生长的影响。1.血管内皮生长因子基因转染头颈部癌细胞系：本实验室建立了不表达血管内皮生长因子的上颌骨癌细胞系，命名为OKK-L。将血管内皮生长因子基因表达载体导入OKK-LN细胞，建立了表达血管内皮生长因子的OKK-LN/pCIneo-VEGF。结果：1.与对照组相比，OKK-LN/pCIneo细胞株表达较强的血管内皮生长因子，OKK-LN/pCIneo细胞仅转染pCIneo质粒。裸鼠皮下注射血管内皮生长因子基因的裸鼠移植瘤细胞株和裸鼠移植瘤细胞系。移植后第35天，血管内皮生长因子转染组(OKK-LN/pCIneo-VEGF；n=6)的肿瘤体积约为对照组(OKK-LN/pCIneo；n=8)的3倍。与对照组相比，血管内皮细胞生长因子转染组的存活时间平均缩短9天。非特异性抑制血管生成因子诱导的血管生成，观察TNP-470、Fumaglin类似物对血管生成的影响。在裸鼠移植OKK-LN/pCIneo-VEGF的同时给予TNP-470。移植后第35天和42天，TNP-470治疗组(n=5)的肿瘤体积较未治疗组(n=5)明显缩小至未治疗组的1/3。TNP-470给药组的生存期明显延长。结论：血管生成对头颈部肿瘤细胞的生长、转移和生存具有重要作用。

Vascular endothelial growth factor (VEGF) gene was transfected to the head and neck cancer cell line and the effect of gene induction on the tumor growth was examined in vitro and in vivo. The results were as follows ;1. VEGF gene transfection to the head and neck cancer cell line.The maxillary cancer cell line expressing no VEGF was established in our department and named as OKK-L N. VEGF gene expressing vector was transfected to OKK-LN cell line, and OKK-LN/pCIneo-VEGF which producing VEGF was established. This ceU line intensively expressed VEGF compared with the control cell line, OKK-LN/pCIneo transfected only pCIneo plasmid.2. Tumor cell growth of the VEGF-transfectd cells transplanted to nude mouse.Both cell lines transplanted to 6 week Balb/c nu/nu mice by subcutaneous injection to right lateral abdomen. Tumor volume of the VEGF-transfected group (OKK-LN/pCIneo-VEGF ; n = 6) showed approximately three times larger than the controlled group (OKK-LN/pCIneo ; n = 8) at Day 35 after the transplantation. The survival of the VEGF-transfected group was shorter by 9 days in average compared to the control group.3. Inhibition of the tumor growth by the angiogenesis suppression factor.The effect of TNP-470, Fumagilin analogue, which nonspecifically inhibits angiogenesis induced by the angiogenesis proliferating factors, such as VEGF and bFGF on the growth of VEGF producing tumor was examined. TNP-470 was simultaneously administered to nude mice at the time of transplantation of OKK-LN/pCIneo-VEGF. Tumor volume of TNP-470 administered group (n = 5) was significantly reduced to one-third compared with non-administered group (n = 5) at Day 35 and Day 42 after the transplantation. And the survival of TNP-470 administered group was significantly prolonged.In conclusion, the angiogenesis plays important roles on cancer cell growth, metastasis and survival in head and neck cancer.