Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8.
Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8.
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发表时间：
2000-10
期刊：
影响因子：
11.2
通讯作者：
Suyun Huang;Jubilee B. Robinson;A. Deguzman;C. Bucana;I. Fidler
中科院分区：
文献类型：
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作者：
Suyun Huang;Jubilee B. Robinson;A. Deguzman;C. Bucana;I. Fidler
我们在原位裸鼠模型中确定了阻断人卵巢癌细胞中核因子（NF）-kappaB/relA 活性是否可以抑制血管生成和生长。人卵巢癌细胞SKOV3ip.1和HEY-A8被突变的IkappaBalpha (IkappaBalphaM)转染，即抵抗磷酸化和降解，从而阻断NF-kappaB活性。 NF-kappaB 信号传导阻断可在体外和体内显着抑制培养细胞和植入裸鼠腹膜腔的细胞中两种主要促血管生成分子（血管内皮生长因子和白细胞介素 8）的表达。血管内皮生长因子和白细胞介素8表达的降低与致瘤性降低、病变血管化减少、恶性腹水形成减少和小鼠生存期延长直接相关。这些发现表明，抑制卵巢癌细胞中的 NF-kappaB/relA 活性可以抑制血管生成和进行性生长。
We determined whether blockade of nuclear factor (NF)-kappaB/relA activity in human ovarian cancer cells can suppress angiogenesis and growth in an orthotopic nude mouse model. The human ovarian cancer cells SKOV3ip.1 and HEY-A8 were transfected with a mutated IkappaBalpha (IkappaBalphaM), ie., resistant to phosphorylation and degradation, and hence blocks NF-kappaB activity. NF-kappaB signaling blockade significantly inhibited in vitro and in vivo expression of two major proangiogenic molecules, vascular endothelial growth factor and interleukin 8, in cultured cells and in cells implanted into the peritoneal cavity of nude mice. The decreased expression of vascular endothelial growth factor and interleukin 8 directly correlated with decreased tumorigenicity, decreased vascularization of lesions, decreased formation of malignant ascites, and prolonged survival of mice. These findings suggest that inhibition of NF-kappaB/relA activity in ovarian cancer cells can suppress angiogenesis and progressive growth.