罗格列酮增强顺铂抑制人肺腺癌细胞增殖作用  

Rosiglitazone enhanced growth inhibition of cisplatin in hunman lung adenocarcinoma cell

作　　者：周亭芳[1] 庄英帜[1] 曹建国[2] 

机构地区：[1]南华大学第一附属医院肿瘤内科,湖南衡阳421001 [2]南华大学肿瘤研究1所,湖南衡阳421001

出　　处：《中国药理学通报》2005年第1期88-91,共4页Chinese Pharmacological Bulletin

摘　　要：目的　探讨过氧化物酶体增殖因子活化受体γ(PPARγ)配体罗格列酮 (Rosiglitazone,RSG)的体外化疗增敏作用及机制。方法　体外培养人肺腺癌A549细胞,MTT法测定药物的细胞生长抑制率,吖啶橙 /溴化乙啶 (AO/EB)荧光双染,流式细胞仪(Flowcytometry,FCM)检测细胞凋亡,免疫细胞化学检测药物处理前后PPARγ,Bcl 2蛋白表达的改变。结果　RSG(1 25, 2 5μmol·L-1 )分别与CDDP合用,可增加CDDP对A549细胞的抑制率, (q> 1 )。RSG(1 25μmol·L-1 )可增强CDDP诱导A549细胞凋亡作用。RSG(1 25μmol·L-1 )处理后,A549细胞的PPARγ蛋白核内表达上调,Bcl 2蛋白表达下调, (P<0 01)。结论　过氧化物酶体增殖因子活化受体γ配体罗格列酮能增强顺铂抑制A549细胞增殖并诱导凋亡作用。PPARγ蛋白核内表达上调,Bcl 2蛋白表达下调在罗格列酮对A549细胞体外化疗增敏作用中发挥重要的作用。目的　探讨过氧化物酶体增殖因子活化受体γ(PPARγ)配体罗格列酮 (Rosiglitazone,RSG)的体外化疗增敏作用及机制。方法　体外培养人肺腺癌A549细胞,MTT法测定药物的细胞生长抑制率,吖啶橙 /溴化乙啶 (AO/EB)荧光双染,流式细胞仪(Flowcytometry,FCM)检测细胞凋亡,免疫细胞化学检测药物处理前后PPARγ,Bcl 2蛋白表达的改变。结果　RSG(1 25,Aim To investigate the synergistic effect of the ligand o f Peroxisome Proliferator-activated Receptor gamma Rosiglitazone with Cisplatin in vitro on human lung adenocarcinoma cell proliferation inhibition and its possible mechanism. Methods Human lung adenocarcinoma A549 cell line was cultured in vitro, cytotoxicity assay was tested by MTT assay. The influ ence of Rosiglitazone with Cisplatin on human lung carcinoma cell apoptosis was detected by PI staning flow cytometry and AO/EB double fluorescence stain. The c hanges of expression of PPARγ and Bcl-2 protein in lung carcinoma cells betwee n untreated and treated with Rosiglitazone were observed by immunohistochemistry . Results Rosiglitazone at various concentrations (1.25, 2.5 μmo l·L -1)enhanced the growth inhibitory effect of Cisplatin to A549 cells( P>1.15). Rosiglitazone at the concentration of 1.25 μmol·L -1 augme nted the induction apoptosis of A549 cells by treatment with Cisplatin at variou s concentrations of 1.98 mg·L -1, 2.8 mg·L -1 and 4.0 mg·L -1 . A549 cells treated with Rosiglitazone at concentration of 1.25 μmol·L -1 domostrated nuclear traslocations of PPARγ protein and down-regulation of Bcl-2 protein. Conclusion The ligand of PPARγ Rosiglitazone enhanc ed the inhibition of proliferation and induction of apoptosis by treatment with Cisplatin in A549 cells cultured in vitro. Activation of PPARγ protein and the down-regulation of Bcl-2 possiblely play an improtant role in chemosenstiz eic mechanism of Rosiglitazone in vitro.

关 键 词：肺肿瘤 罗格列酮 顺铂 化疗增敏剂 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学]