Sirtinol对胰腺癌PANC-1细胞增殖和5-FU敏感性的影响  

Effects of Sirtinol on proliferation and 5-FU chemosensitivity of pancreatic cancer PANC-1 cells

作　　者：张军港[1] 石英[2] 王知非[1] 洪德飞[1] 

机构地区：[1]浙江省人民医院肝胆胰外科,浙江省杭州市310014 [2]浙江省人民医院妇产科,浙江省杭州市310014

出　　处：《世界华人消化杂志》2014年第1期86-90,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨沉默信息调节因子-1(silent information regulator 1,SIRT1)去乙酰化酶抑制剂Sirtinol体外应用对胰腺癌PNAC-1细胞增殖和5-FU化疗敏感的影响.方法:应用不同浓度的Sirtinol(25,50和100μmol/L)处理PNAC-1细胞48 h,Western blot测定SIRT1表达的变化情况,MTT法检测PANC-1细胞增殖变化,流式细胞术观察细胞凋亡变化,MTT法检测Sirtinol对5-氟尿嘧啶(5-fluorouracil,5-FU)化疗敏感性的变化.结果:Sirtinol显著降低SIRT1的表达量,明显抑制了PANC-1细胞的增殖,促进了凋亡,且呈浓度依赖性.与Sirtinol(A=0.546±0.020)或5-FU(A=0.526±0.023)单药作用相比,两药联合应用可显著降低PANC-1细胞的增殖(A=0.251±0.017,P<0.01).结论:Sirtinol通过下调SIRT1表达可抑制胰腺癌细胞增殖和促进其凋亡,同时增强化疗药5-FU敏感性,这为胰腺癌的化疗提供了一种新的方案.AIM： To investigate the effects of SIRT1 specific inhibitor Sirtinol on proliferation and 5-FU chemosensitivity of pancreatic cancer PANC-1 cells. METHODS： PANC-1 cells were treated with 25, 50 and 100 μmol/L Sirtinol for 48 h. The expression levels of SIRT1 were measured by Western blot. Cell proliferation was detected by MTT assay. Cell apoptosis was detected by flow cytometry （FCM）. 5-FU chemosensitivity was measured by MTT assay. RESULTS： Sirtinol obviously decreased the expression of SIRT1, inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner. Moreover, compared with Sirtinol alone （A = 0.546 ± 0.020） or 5-FU alone （A = 0.526 ± 0.023）, Sirtinol combined with 5-FU more significantly inhibited the proliferation of PANC-1 cells （A = 0.251 ± 0.017, both P 〈 0.01）. CONCLUSION： Sirtinol could induce cell proliferation inhibition and apoptosis, and enhance anti-cancer effects of chemotherapy on PANC-1 cells possibly via mechanisms associated with down-regulating SIRT1 expression.

关 键 词：胰腺癌 Sirtinol 5-氟尿嘧啶 增殖 凋亡 

分 类 号：R735.9[医药卫生—肿瘤]