γ分泌酶抑制剂DAPT对胰腺癌细胞生长的影响  

Suppressive Effects of γ-secretase Inhibitor DAPT on the Proliferation of Pancreatic Cancer Cells

作　　者：杜潇[1] 程中[1] 李旸[1] 周总光[1] 杨烈[1] 张明鸣[1] 

机构地区：[1]四川大学华西医院胃肠外科中心,成都610041

出　　处：《四川大学学报（医学版）》2013年第5期699-702,共4页Journal of Sichuan University(Medical Sciences)

基　　金：中央高校基本科研业务费(No.2011SCU11050);四川省科技支撑计划(No.2011SZ0293)资助

摘　　要：目的探讨γ分泌酶抑制剂DAPT对人胰腺癌细胞生长的影响及其可能机制。方法选用胰腺癌细胞株AsPC-1、BxPC-3、MIAPaCa-2作为实验研究对象,应用不同剂量(100μmol/L,50μmol/L,10μmol/L)的DAPT作用不同时间后,CCK-8法检测细胞增殖,Annexin V/PI双染法检测细胞凋亡。结果与空白对照组相比,100μmol/L DAPT作用时3株胰腺癌细胞从3d开始出现增殖抑制(P<0.05);50μmol/L DAPT作用时AsPC-1细胞在5d出现增殖抑制(P<0.05),BxPC-3和MIAPaCa-2细胞在3~5d出现了抑制(P<0.05);10μmol/L DAPT作用时仅BxPC-3和MIAPaCa-2细胞在5d出现了生长抑制(P<0.05)。流式细胞术显示DAPT作用组细胞凋亡率较空白对照组增加。结论应用DAPT阻断Notch信号通路可通过促进胰腺癌细胞凋亡而抑制胰腺癌生长。Objective To explore the effect of DAPT,aγ-secretase inhibitor on the proliferation of pancreatic cancer cells and its underlying mechanism.Methods Three human pancreatic cancer cell lines as AsPC-1,BxPC-3 and MIAPaCa-2 were employed for in vitro experiments.Cell proliferation was tested by CCK-8 and cell apoptosis was examined by Annexin V/PI staining after the treatment of various concentrations of DAPT at different time.Results DAPT of 100μmol/L significantly inhibited the proliferation of these 3cell lines from day 3 to 5.DAPT of 50μmol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2cells from day 3 to 5,whereas the effect of inhibition was only observed at day 5in AsPC-1cell.DAPT of 10μmol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2cells at day 5,whereas no effect was found in AsPC-1.Flow cytometry test showed that cell apoptosis rate was higher in DAPT treatment groups compared with control group.Conclusion DAPT could suppress the proliferation of pancreatic cancer cell,with the mechanism of promoting cell apoptosis.

关 键 词：胰腺癌 γ分泌酶抑制剂 DAPT NOTCH信号通路 凋亡 

分 类 号：R735.9[医药卫生—肿瘤]