c-fos反义脱氧寡核苷酸阻断VIP诱导的VEGF在小细胞肺癌细胞中表达  

c-fos antisense oligodeoxynucleotide reduces VIP-induced upregulation of VEGF expression in small cell lung cancer cells

作　　者：赵正源[1] 程庆书[1] 李小飞[1] 王小平[1] 刘锟[1] 

机构地区：[1]第四军医大学唐都医院胸外科,西安710038

出　　处：《中国肺癌杂志》2006年第4期312-315,共4页Chinese Journal of Lung Cancer

摘　　要：背景与目的血管活性肠肽(VIP)对多种肿瘤细胞的生长具有促进作用,但其作用机制尚有许多未解之处。本研究旨在通过抑制c-fos基因表达,探讨其表达产物是否参与VIP对小细胞肺癌(SCLC)细胞中血管内皮生长因子(VEGF)mRNA表达的调节作用。方法应用RT-PCR技术检测VIP作用下SCLC细胞系H446中c-fos及VEGF基因表达水平,以c-fos反义脱氧寡核苷酸(ASO)封闭c-fos基因表达,检测不同c-fos表达水平条件下VIP对VEGF表达的调节作用。结果VIP增强了c-fos及VEGF在H446细胞中的表达。c-fosmRNA的表达在VIP作用2h和4h时达到高峰,显著高于VIP作用0h时(P<0.01)。在VIP作用8h和16h时,VEGF mRNA的表达水平达到高峰,显著高于VIP作用0h时(P<0.01)。c-fosASO能明显反转VIP诱导的VEGF的表达上调(P<0.01)。结论VIP可能通过增强转录因子c-fos的表达,进而促进VEGF mRNA在肺癌细胞中的表达和分泌,促进肺癌新生血管的生成,参与肿瘤的生长。Background and objective It has been known that vasoactive intestinal peptide （VIP） has the effect of promoting the growth of some malignant tumors, but its mechanism is not clear. The aim of this study is to use c-fos antisense oligodeoxynucleotide （ASO） to block c-fos expression and to explore whether c- fos can directly regulate VIP-induced VEGF expression in small cell lung cancer （SCLC） cells. Methods Expression levels of c-fos and VEGF genes were detected in SCLC cell line H446 treated with VIP by RT-PCR. After c-fos ASO was added to the H446 cells, the change of VEGF mRNA expression level was analyzed. Resuits Administration of VIP resulted in increased expression of c-fos and VEGF mRNA in the H446 cells. The expression of c-fos mRNA reached the peak level at 2 h and 4 h after VIP treatment, which was significantly higher than that at 0 h （P〈0.01）. Whereas, the highest expression level of VEGF mRNA was observed at 8 h and 16 h after VIP treatment, which was significantly higher than that at 0 h （P〈0.01）. c-fos ASO significantly reversed VIP-induced upregulation of VEGF mRNA expression （P〈0. 01）. Conclusion VIP can increase the expression and secretion of VEGF in lung cancer cells by activating the transcription factor c-fos, then promote the angiogenesis of lung cancer and thus play an important role in the pathogenesis of lung cancer.

关 键 词：小细胞肺癌 血管活性肠肽 C-FOS 血管内皮生长因子 反义脱氧寡核苷酸 血管形成 

分 类 号：R734.2[医药卫生—肿瘤]