ICI118,551诱导胰腺癌细胞凋亡及其机制的实验研究  

The Apoptosis of Human Pancreatic Cancer induced by ICI118, 551 and Its Mechanism of Action

作　　者：徐军[1] 彭波[2] 穆维靖[1] 王铮[1] 张东[1] 马清涌[1] 

机构地区：[1]西安交通大学医学院第一附属医院肝胆外科,陕西西安710061 [2]西安交通大学医学院第一附属医院急诊科,陕西西安710061

出　　处：《昆明医科大学学报》2012年第8期21-26,共6页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(81172195)

摘　　要：目的研究ICI118,551通过调控细胞信号通路抑制抗凋亡分子的表达所产生的促凋亡效应及其机制.方法应用β2受体阻滞剂ICI118,551和β1受体阻滞剂美托洛尔干预胰腺癌细胞,通过电镜检测细胞凋亡、Hoechst 33324荧光染色检测细胞凋亡、流式细胞仪检测细胞凋亡、Western blot等技术检测β2受体阻滞剂对ERK和Akt磷酸化改变,调节细胞凋亡和细胞周期下游相关分子caspase-3、caspase-9、Bcl-2及Bax的表达.结果 ICI118,551可显著诱导胰腺癌细胞凋亡,细胞凋亡率显著大于美托洛尔组(P<0.05);ICI118,551干预组抑制Akt和ERK的磷酸化,并激活Bax、caspase-3和caspase-9活性片段的表达,同时抑制Bcl-2的表达.结论β2受体阻滞剂可以阻断相关细胞通路而进一步抑制下游相关促侵袭和抗凋亡分子的表达,并产生促凋亡效应.Objective To investigate the effect of ICI118,551 on pancreatic cancer cell apoptosis and its action mechanism.Methods The apoptotic index was determined by the flow cytometry assay.The cell morphology of apoptosis was observed by electron microscope and Hoechst 33324 fluorescein stain.The expression of ERK,Akt,caspase-3,caspase-9,Bcl-2 and Bax was analysed by Western blot.Results ICI118,551 significantly induced apoptosis compared with β1-adrenergic antagonist metoprolol in MIA PaCa-2 and BxPC-3 cell lines.ICI118,551 affected the expression of ERK,Akt,caspase-3,caspase-9,Bcl-2 and Bax.Conclusion β2 adrenoceptor antagonist can block related cell signal pathways,then inhibit the expression of pro-invasive and anti-apoptotic factors in the downstream,and finally induce the apoptosis of pancreatic cancer cell.

关 键 词：β2受体阻滞剂ICI118 551 凋亡 G1/S期阻滞 

分 类 号：R735.9[医药卫生—肿瘤]