人头颈鳞状细胞癌中血管内皮生长因子的反义抑制作用
Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma.
作者信息
Nakashima T, Hudson J M, Clayman G L
机构信息
Department of Head and Neck Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
出版信息
Head Neck. 2000 Aug;22(5):483-8. doi: 10.1002/1097-0347(200008)22:5<483::aid-hed7>3.0.co;2-h.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent paracrine angiogenic factor involved in angiogenesis. We determined whether antisense VEGF transfection can suppress angiogenic activity of a human squamous cell carcinoma of the head and neck (SCCHN) cell line.
METHODS
Human SCCHN cell lines were screened for VEGF secretion by ELISA. The highest VEGF secreting cell line was transfected with an antisense VEGF vector. Endothelial cell migration assays were performed using the conditioned medium from the transfected clones. Tumorigenicity assays of the transfectants in nude mice were also performed.
RESULTS
Antisense VEGF expression exhibited a 20-fold inhibition of VEGF secretion. The addition of conditioned medium from the antisense clones resulted in 50% reduction of endothelial migration. There was no effect on in vivo tumorigenicity.
CONCLUSIONS
Antisense VEGF transfection effectively down-regulated VEGF secretion from SCCHN cells that had high VEGF secretion. Targeting VEGF expression may be useful for suppressing angiogenesis in head and neck cancer.
背景
血管内皮生长因子（VEGF）是一种参与血管生成的强效旁分泌血管生成因子。我们确定了反义VEGF转染是否能抑制人头颈鳞状细胞癌（SCCHN）细胞系的血管生成活性。
方法
通过酶联免疫吸附测定（ELISA）筛选人SCCHN细胞系的VEGF分泌情况。用反义VEGF载体转染VEGF分泌量最高的细胞系。使用转染克隆的条件培养基进行内皮细胞迁移试验。还对转染子在裸鼠中的致瘤性进行了检测。
结果
反义VEGF表达对VEGF分泌有20倍的抑制作用。添加反义克隆的条件培养基使内皮细胞迁移减少了50%。对体内致瘤性没有影响。
结论
反义VEGF转染有效下调了高VEGF分泌的SCCHN细胞的VEGF分泌。靶向VEGF表达可能有助于抑制头颈癌中的血管生成。
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