17-丙烯胺-17-去甲氧格尔德霉素对胆管癌细胞株QBC939生长周期及凋亡的影响  

Effects of 17-allylamino-17.demethoxygeldanamycin on the growth cycle and apoptosis of bile duct cancer cell line QBC939

作　　者：石铮[1] 陈志山[2] 陈有挺[1] 何庆良[1] 

机构地区：[1]福建医科大学附属第一医院普外科,福州350005 [2]福建医科大学

出　　处：《中华实验外科杂志》2008年第10期1237-1239,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察热休克蛋白90（HSP90）抑制剂17-丙烯胺-17-去甲氧格尔德霉素（17-AAG）对胆管癌细胞生长的影响。方法应用噻唑蓝（MTT）比色法观察17-AAG对胆管癌细胞系QBC939细胞的生长抑制作用；用流式细胞术分析细胞凋亡及细胞周期变化；瑞特吉姆染色法观察细胞形态学；细胞免疫组织化学检测药物处理前后QBC939细胞CDK1和C-e-rbB2的表达变化。结果17-AAG呈时间、剂量依赖性抑制QBC939细胞，48h半数抑制浓度（IC50）为1．0umol／L；经17-AAG作用36h后细胞阻滞于G2期从（11．90±0．78）％上升到（40．33±0．91）％，伴有S期细胞减少；17-AAG处理48h后早期凋亡明显增加；同时17-AAG处理后的CDKl和C-erbB-2的表达明显减少。结论HSP90抑制剂17-AAG通过抑制HSP90的分子伴侣功能，下调CDKl和C-erbB2表达，从而抑制细胞增殖，诱导细胞凋亡和周期阻滞。Objective To study the effects Of heat shock protein 90 （HSP90） inhibitors 17-al- lylamino-17-demethoxygeldanamycin（17-AAG） induced bile duct cancer cell growth and related mecha- nisms. Methods MTT assay was used to detect the growth inhibition of QBC939 cells. Cell cycle and apoptosis were analyzed by flow cytometry. The cell morphology was observed with Wright-Giemsa attaining. Alteration of CDK1 and C-e-rbB2 being treated with 17-AAG were measured by immunohistochemistry. Results 17-AAG significantly inhibited growth of QBC939 ceils in vitro in a dose-dependent manner with an IC50 value at 1.0 μmol/L. Exposure for 36 hours, 17-AAG causes cycle arrested at the G2 phase from 1l. 90± 0.78 percent to 40.33±0.9l percent,with S-phase reduction. Exposure for 48 hours, 17-AAG causes cell apoptosis. The level of CDK1 and C-e-rbB2 expression in QBC939 cells being treated with 17- AAG,compared to that in control cells,was reduced significantly. Conclusion 17-AAG inhibits Hsp90 chaperone function, and reduces CDK1 and C-erbB2 expression,inhibiting cell proliferation and induceing Cell cycle arrest and apoptosis.

关 键 词：胆管癌 HSP90 17-AAG 细胞凋亡 C-erbB.2 CDKl 

分 类 号：R735.8[医药卫生—肿瘤] R285.5[医药卫生—临床医学]