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

将血管内皮生长因子（Vascular endothelial growth factor， VEGF）基因转染头颈部肿瘤细胞系，在体外和体内观察其对肿瘤生长的影响。实验结果如下：1.实验结果表明：VEGF基因转染头颈部癌细胞系。我科建立了不表达VEGF的上颌癌细胞株，命名为OKK-L N.将VEGF基因表达载体转染到OKK-LN细胞株上，建立了产生VEGF的OKK-LN/pCIneo-VEGF。与对照细胞系相比，该ceU细胞系强烈表达VEGF， OKK-LN/pCIneo仅转染pCIneo质粒。vegf转染细胞移植裸鼠肿瘤细胞生长情况。两种细胞系均经右外侧腹腔皮下注射移植至6周龄Balb/c nu/nu小鼠。移植后第35天，vegf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。vegf转染组的生存期比对照组平均短9天。血管生成抑制因子对肿瘤生长的抑制作用。研究了非特异性抑制血管生成增殖因子VEGF和bFGF诱导的血管生成的富马吉林类似物TNP-470对VEGF生成肿瘤生长的影响。裸鼠移植OKK-LN/pCIneo-VEGF时同时给予TNP-470。在移植后第35天和第42天，TNP-470给药组（n = 5）的肿瘤体积显著减少至未给药组（n = 5）的三分之一。TNP-470给药组的生存期明显延长。综上所述，血管生成在头颈部肿瘤细胞的生长、转移和存活中起着重要作用。

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.