BAY11-7082对5-氟尿嘧啶的抑制胰腺癌细胞增殖及诱导凋亡的影响  

The research of BAY11-1082 on inhibition and inducing apoptosis in pancreatic carcinoma of 5-fluorouracil

作　　者：胡明星[1] 付强[1] 刘传江[1] 王玉柱[1] 秦涛[1] 

机构地区：[1]郑州大学人民医院肝胆胰腺外科,450003

出　　处：《中华实验外科杂志》2014年第3期550-552,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（31140078、30972928）

摘　　要：目的 观察核转录因子-κB（NF-κB）抑制剂BAY11-7082对胰腺癌细胞增殖及对不同浓度5-氟尿嘧啶（5-Fu）诱导胰腺癌细胞凋亡的影响.方法 人胰腺癌细胞SW1990经5μmoL/LNF-κB抑制剂BAY11-7082预处理1h后,Western blot法检测磷酸化NF-κB p65蛋白表达量.加入含有50、200 μg/L、1.0 mg/L 5-Fu的培养基,未经处理组作为对照,噻唑蓝（MTT）法检测各组胰腺癌细胞的抑制率,实时定量逆转录聚合酶链反应（RT-qPCR）检测抗凋亡基因B细胞淋巴瘤/白血病-2（bcl-2） mRNA表达量,Western blot法检测抗凋亡基因bcl-2基因蛋白表达量,流式细胞术检测24 h胰腺癌细胞的凋亡率.结果 经BAY11-7082预处理1h后磷酸化NF-κB p65蛋白表达量较对照组明显降低.不同浓度的5-Fu作用下,经BAY11-7082预处理的各组胰腺癌细胞抑制率较对照组均明显升高（P＜0.05）.bcl-2基因mRNA表达量（0.75±0.09、0.52 ±0.01、0.41±0.06）较对照组（0.92 ±±0.01、0.81±0.05、0.72±0.01）均明显降低（P＜0.05）,bcl-2蛋白表达量较对照组明显降低,胰腺癌细胞的凋亡率[（16.79±1.23）％、（26.82±1.26）％、（38.20±5.89）％]较对照组[（8.64±0.30）％、（14.02±0.32）％、（24.13±1.60）％]明显增高（P＜0.05）.结论 BAY11-7082能通过抑制NF-κB的活化,增加5-Fu抑制胰腺癌细胞SW1990的增殖及诱导胰腺癌SW1990细胞的凋亡.Objective To study the influence of BAY11-7082 [nuclear factor-kappa B （NF-κB）inhibitor] on the inhibition and inducing apoptosis in pancreatic carcinoma of 5-fluorouracil （5-Fu）.Methods The human pancreatic carcinoma SW1990 cells were deal with 5 μmoL/L BAY11-7082 for 1 h before the cells were exposure to 5-Fu.Western blotting was used to detected the phosphoryltion NF-κB p65.After the cells were exposure to 50,200 μg/L,1.0 mg/L 5-Fu,methyl thiazol tetrazolium （MTT）was used to detect the inhibition rate and real-time reverse transcriptase-polymerase chain reaction （RT-qPCR） was used to detect the expression mRNA of anti-apoptosis gene B cell lymphoma/leukemia-2 （bcl-2）.The level of bcl-2 protein was detected by using Western blotting and flow cytometry was used to detect the apoptosis rate of SW1990.Results After the effect of nuclear factor-kappa B （BAY11-7082）,the expression of phosphoryhion NF-κB p65 was decreased obviously.The effect of MTT showed that the inhibition rate of 5-Fu on SW1990 elevated significantly compared with the control groups （P ＜ 0.05）.The expression of bcl-2 reduced obviously in protein and mRNA level （P ＜ 0.05）.The apoptosis rate the groups that was exposure to BAYll-7082 were （16.79 ± 1.23）％,（26.82 ± 1.26）％,（38.20 ±5.89）％,which elevated significantly compared with control groups （8.64 ± 0.30）％,（14.02 ±0.32）％,（24.13± 1.60）％,（P＜0.05）.Conclusion The level of phosphorylation NF-κB p65 reduced after the effect of BAY11-7082,which might increase the sensitivity of SW1990 to 5-Fu and elevate the apoptosis rate of SW1990 after the effect of 5-Fu.

关 键 词：胰腺癌 核转录因子-κB抑制剂 5-氟尿嘧啶 凋亡 

分 类 号：R735.9[医药卫生—肿瘤]