NF-κB圈套寡脱氧核苷酸联合紫杉醇对肺癌血管生成的影响

Effects of NF-κB decoy oligonucleotide combined with paclitaxel on angiogenesis in lung cancer.

目的探讨NF-κB圈套寡脱氧核苷酸技术(NF-κB decoy ODN)联合紫杉醇对肺癌血管生成的影响。方法培养人肺癌细胞A549:(1)用脂质体瞬时转染法介导NF-κB全硫代圈套寡核苷酸(decoy ODN)和全硫代错义圈套寡核苷酸(scramble decoy ODN)处理A549细胞;(2)分为对照组、NF-κB decoy ODN组、紫杉醇组(1 000 ng/mL)和NF-κB decoy ODN+紫杉醇组,RT-PCR法测COX-2 mRNA水平表达;(3)免疫组织化学法测VEGF蛋白表达。结果 NF-κB decoy ODN、紫杉醇干预后A549细胞的COX-2 mRNA水平表达下降,对照组、NF-κB decoy ODN组、紫杉醇组、NF-κB decoy ODN+紫杉醇组浓度依次是:(0.71±0.04)μg/μL、(0.44±0.08)μg/μL、(0.51±0.02)μg/μL、(0.34±0.05)μg/μL(P<0.05)。VEGF蛋白表达亦下降,各组细胞阳性率依次是:(85±0.50)%、(63±0.26)%、(57±1.5)%、(21±0.34)%(P<0.05)。结论 NF-κB decoy ODN联合紫杉醇可明显抑制肺癌细胞血管生成,该作用可能与COX-2、VEGF表达相关。

Objective To investigate the effects of NF-κB decoy oligodeoxynucleotide technology（NF-κB decoy ODN） combined with paclitaxel on angiogenesis in lung cancer.Methods Human lung cancer cell A549 was cultured.Full phosphorothioate NF-κB decoy Oligonucleotides（decoy ODN） and all missense decoy phosphorothioate oligonucleotides（scramble decoy ODN） were transfected with liposome-mediated technique into A549 cells.Treated A549 cells were assigned into control group,NF-κB decoy ODN group,paclitaxel group and NF-κB decoy ODN plus paclitaxel group.RT-PCR and immunohistochemical methods were applied to measure cyclooxygenase-2（COX-2） mRNA expression level and vascular endothelial growth factor（VEGF） protein expression.Results Either NF-κB decoy ODN or paclitaxel intervention had significantly lowered both COX-2 mRNA and VEGF protein expression in A549 cells（P〈0.05）.Futhermore,expression levels of COX-2 mRNA in each group were（0.71±0.04）μg/μL、（0.44±0.08）μg/μL、（0.51±0.02）μg/μL、（0.34±0.05）μg/μL,respectively（P〈0.05）,while the VEGF positive rates were（85±0.50）%、（63±0.26）%、（57±1.5）%、（21±0.34）%,respectively（P〈0.05）.Conclusion NF-κB decoy ODN plus paclitaxel treatment inhibits angiogenesis in lung cancer,which is related to reduced lowering of COX-2 and VEGF expression.