ICI118551联合吉西他滨对胰腺癌细胞BxPC-3增殖和凋亡的影响及其机制  

Effect and mechanisms of ICI 118551 combined with gemcitabine on the proliferation and apoptosis of BxP C-3 cells

作　　者：单涛[1] 徐军[1] 刘江波[1] 李军涛[1] 李彬[1] 段万星[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

出　　处：《西安交通大学学报（医学版）》2012年第3期336-339,364,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省13115科技攻关项目资助(No.2010ZDKG-49)~~

摘　　要：目的探讨β2肾上腺素能受体阻滞剂ICI 118551与吉西他滨联合应用对胰腺癌细胞BxPC-3增殖和凋亡的影响及可能的机制。方法利用ICI 118551、吉西他滨及ICI 118551+吉西他滨干预胰腺癌细胞BxPC-3,MTT法检测细胞增殖能力,Annexin V-FITC/PI和TUNEL检测细胞凋亡情况,RT-PCR检测Bax、Bcl-2表达,Western blot检测NF-κB亚基P65、Bax、Bcl-2表达变化。结果 ICI 118551明显增强吉西他滨的抗增殖和促凋亡效应,成功阻断由吉西他滨诱导的NF-κB的活化,并且提升了Bax/Bcl-2mRNA和蛋白的表达。结论 ICI 118551能增强吉西他滨对胰腺癌细胞的抑制作用,提示吉西他滨联合β2肾上腺素能受体阻滞剂可作为胰腺癌治疗的一种有效方法。Objective To investigate the anti-proliferative effects of β2-adrenoceptor blocker ICI 118551,gemcitabine and ICI 118551 + gemcitabine on BxPC-3 cells and further analyze the underlying mechanisms.Methods MTT was used to detect the anti-proliferative effect of ICI 118551,gemcitabine and ICI 118551 + gemcitabine on BxPC-3 cells.The apoptosis index was determined using TUNEL,and Annexin V and fluorescein isothiocyanate/propidium iodide flow cytometry assay,respectively.Expressions of Bcl-2 and Bax mRNA were detected by RT-PCR.Protein levels of Bcl-2,Bax and NF-κB subunit P65 were analyzed by Western blotting.Results ICI 118551,gemcitabine and ICI 118551 + gemcitabine could suppress proliferation of BxPC-3 cells.ICI 118551 + gemcitabine showed a higher apoptosis rate induction than ICI 118551 or gemcitabine alone.When cells were treated with gemcitabine in combination with ICI 118551,NF-κB activation was blocked;the expression of Bax/Bcl-2 protein was substantially increased.Conclusion ICI 118551 combined with gemcitabine has a synergistic anticancer effect on BxPC-3 cells,and the combination may be an effective therapeutic strategy for pancreatic cancer.

关 键 词：吉西他滨 β2上腺素能受体阻滞剂 胰腺癌 凋亡 ICI118551 增殖 

分 类 号：R735[医药卫生—肿瘤]