细胞因子和低氧对胰腺癌细胞表达血管内皮生长因子A、C的调节  

Regulation of expression of vascular endothelial growth factor A and C by cytokines and hypoxia in pancreatic cancer cells

作　　者：唐瑞峰[1] 王曙霞[2] 彭利[1] 王顺祥[1] 张萌[1] 肖燕[1] 张风瑞[1] 

机构地区：[1]河北医科大学第四医院肝胆外科,石家庄050011 [2]河北医科大学第四医院皮肤科,石家庄050011

出　　处：《肿瘤》2007年第1期30-33,共4页Tumor

基　　金：教育部留学回国人员科研启动基金资助项目[编号:教外司留(2002)247号]

摘　　要：目的：探讨细胞因子白细胞介素（IL）-1α、IL-6、肿瘤坏死因子（TNF）α、SNAP（S-nitroso—nacetyl—penicillamine）（在培养细胞中可释放N0，使细胞处于低氧状态）对胰腺癌细胞产生和分泌血管内皮生长因子（VEGF）-A、C的调节。方法：用northernblot和western blot法分别分析人胰腺癌细胞株中VEGF-A、VEGF-C基因和蛋白的表达；以IL-1α（10μg／L）、IL-6（100μg／L）、TNFα（50μg／L）或SNAP（25mg／L）刺激细胞株后用逆转录-聚合酶链式反应技术（RT—PCR）分析其VEGF-A、VEGF-C基因的表达。结果：Northern blot法显示6种胰腺癌细胞株均有4．1 kb VEGF—A基因和2．4 kb VEGF—C基因的表达；Western blot法显示这6种胰腺癌细胞株均有相对分子质量为43×10^3的VEGF-A蛋白和相对分子质量为55×10^3的VEGF-C蛋白表达。RT-PCR分析法显示：IL-1α使细胞株COL0-357产生VEGF-A、VEGF-CmRNA分别增加1～2倍、1倍；IL-6刺激细胞株CAPAN-1产生VEGF-A、VEGF-CmRNA分别增加2～5倍、1倍；TNF-α使细胞株COL0-357产生VEGF-A、VEGF-CmRNA分别减少1～2．5倍、1～2倍，使细胞株CAPAN-1产生VEGF-A、VEGF-CmRNA分别减少1倍、1．6～2．5倍；而SNAP刺激细胞株COL0-357产生VEGF-A mRNA增加5倍，刺激细胞株CAPAN-1产生VEGF-Am RNA增加4倍。结论：细胞因子IL-1α、IL-6、TNFα和SNAP通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性。Objectire：To explore the regulation of production and secretion of vascular endothelial growth factor （VEGF） A and C in cultured human pancreatic cancer cell lines by cytokines such as interleukin（IL）-1α, IL-6, and tumor necrosis factor （TNF）a and S-nitroso-nacetyl-penicillamine （SNAP, NO donor, induce hypoxia in the culture medium）. Methods：The mRNA expression of VEGF A and C were detected by Northern blot and protein expression was measured by Western blot in 6 cell lines （ASPC-1, CAPAN-1, MIA-PaCa2, PANC-1, COLO-357, and T3M4）. VEGF A and C expressions in cultured CAPAN-1 and COLO-357 cells were analyzed by reverse-transcription polymerase chain reaction （RT-PCR） after stimulation with IL-la （10 μg/L）, IL-6 （100 μg/L）, TNFa（50 μg/L）, or SNAP （25 mg/L）. Results：Northern blot analysis revealed the expressions of the 4.1 kb VEGF-A mRNA transcript and 2.4 kb VEGF-C mRNA transcript in all 6 tested cell lines. Western blot showed the expression of 43 × 10^3 VEGF-A protein and 55 × 10^3 VEGF-C protein in the 6 cell lines. RT-PCR analysis showed that the levels of VEGF-A mRNA had 1-2 fold increase and VEGF-C mRNA had 1 fold increase in COLO-357 cells after IL-lα stimulation. The levels of VEGF-A mRNA had 2-5 fold increase and VEGF-C mRNA had 1 fold increase in CAPAN-1 cells after IL-6 stimulation. TNFa stimulation caused 1-2.5 fold decrease of VEGF-A mRNA and 1-2 fold decrease of VEGF-C mRNA in COLO- 357 cells and caused 1 fold decrease of VEGF-A mRNA and 1.6-2.5 fold decrease of VEGF-C mRNA in CAPAN-1 cells. SNAP stimulated 5 fold increase of VEGF-A mRNA in COLO-357 cells and 4 fold increase of VEGF-A mRNA in CAPAN-1 cells. Conclusion：IL-lα, IL-6, TNFa, and SNAP influence the biological properties of pancreatic cancer cells by regulating expression of VEGF-A and VEGF-C.

关 键 词：胰腺肿瘤 白细胞介素1Α 白细胞介素6 肿瘤坏子因子 低氧 血管内皮生长因子类 

分 类 号：R735.9[医药卫生—肿瘤]