HSP90抑制剂17-DMAG调控胰腺癌细胞PANC-1增殖及凋亡的初步研究  

Heat shock protein 90 inhibitor,17-DMAG,suppresses proliferation and induces apoptosis in pancreatic cancer cells in vitro

作　　者：赖明广[1] 姚君[1] 王立生[1] 

机构地区：[1]暨南大学第二临床医学院消化内科,广东深圳518020

出　　处：《第三军医大学学报》2013年第7期627-629,共3页Journal of Third Military Medical University

基　　金：广东省自然科学基金(10151802001000002)~~

摘　　要：目的探讨热休克蛋白90(HSP90)功能特异性抑制剂17-DMAG对胰腺癌细胞PANC-1增殖与凋亡的影响。方法体外培养腺癌细胞PANC-1,17-DMAG处理PANC-1细胞后,CCK8法测定细胞生长曲线,观察细胞增殖的抑制情况,流式细胞仪测定细胞凋亡率的变化,Jc-l染色检测线粒体膜电位变化,RT-PCR法测定17-DMAG处理PANC-1细胞前后Bcl-2、Bax表达变化。结果 17-DMAG处理组24 h时D(490)值较对照组差异无统计学意义(P>0.05),48、72 h后较对照组D(490)值分别减少(18.3±2.4)%、(21.5±3.2)%,差异有统计学意义(P<0.05)。17-DMAG处理组48 h时较对照组能显著地抑制PANC-1细胞增殖(P<0.05),细胞凋亡率[(22.4±2.4)%]较对照组[(4.2±1.7)%]显著增加(P<0.05);线粒体电位显著降低(P<0.05)。RT-PCR结果显示,17-DMAG处理组抑制Bcl-2的表达,促进Bax的表达。结论 17-DMAG可抑制胰腺癌细胞PANC-1增殖并诱导其凋亡,该效应可能是通过调控凋亡相关蛋白Bcl-2家族成员的表达实现。Objective To determine the effect of 17-dimethylaminoethylamino-17-demethoxy geldana- myein （ 17-DMAG）, a specific inhibitor of heat shock protein 90 （HSP90）, on the proliferation and apoptosis in pancreatic cancer cell line PANC-1. Methods After PANC-1 cells were treated with 17-DMAG at the final dose of 500 nmol/mL, CCK8 assay was used to plot cell growth curve. Flow cytometry was used to detect the cell cycle and apoptosis. JC-1 mitochondrial membrane potential assay kit was applied to detect mitochondrial membrane potential. Reverse transcription polymerase chain reaction （RT-PCR） was applied to detect the mRNA expression of Bcl-2 and Bax. Results 17-DMAG treatment for 24 h resulted in no significant differ- ence in cell growth in PANC-1 cells （P 〉 0.05 ）, but when the treatment was prolonged to 48 and 72 h, the growth was decreased by （18.3±2.4）% and （21.5 ±3.2）%, respectively （P 〈0.05）. After 17-DMAG treatment for48 h, the proliferation was obviously inhibited in 17-DMAG group than in control group （P 〈 O. 05 ）, with its apoptotic rate significantly higher [ （22.4 ±2.4 ） % vs （4.2 ± 1.7 ） %, P 〈 0.05 ], and the mitochondrial membrane potential significantly decreased （ P 〈 0.05 ）. 17-DMAG down-regulated the mRNA level of Bcl-2, and consequently up-regulated that of Bax in PANC-1 cells. Conclusion 17-DMAG inhibits the proliferation and induces the apoptosis in PANC-1 cells by regulating apoptosis-related protein Bcl-2 family.

关 键 词：17-DMAG 增殖 凋亡 PANC-1 

分 类 号：R73-36[医药卫生—肿瘤] R735.9[医药卫生—临床医学]