17β雌二醇、他莫昔芬和雷洛昔芬诱导前列腺癌细胞凋亡及细胞周期阻滞的研究  

Proliferation inhibition and apoptosis onset in human prostate carcinoma cell line PC3 induced by 17β-estradiol,tamoxifen and raloxifene

作　　者：张宇曦[1] 孔垂泽[1] 李振华[1] 崔军[1] 安康[2] 刘树民[2] 张崇伦[2] 刘鹏[2] 王雪松[2] 

机构地区：[1]中国医科大学第一医院泌尿外科,沈阳110001 [2]辽宁省人民医院泌尿外科

出　　处：《中华实验外科杂志》2006年第12期1526-1528,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨17β雌二醇(E2)、他莫昔芬(TAM)和雷洛昔芬(RAL)对前列腺癌PC3凋亡、细胞周期的影响及作用机制。方法检测不同浓度E2、TAM、RAL作用于PC3细胞不同时间后细胞生长抑制率和48 h后细胞周期分布、凋亡率、bcl-2和Caspase-3蛋白的表达,以及12 h后p21WAF1 mRNA．表达。Hoechst染色和电镜观察细胞凋亡。结果E2、TAM、RAL呈时间及浓度依赖性抑制PC3细胞增殖。10-4 mol／L E2、10-5 mol／L TAM和10-5 mol／L RAL作用48 h后检测到凋亡,凋亡率分别为(21．54±0．91)％、(38．28±1．16)％、(42．41±2．26)％(P<0．05),bcl-2和Caspase-3分别为对照组的0．5、0．4、0．35倍;1．4、1．6、1．6倍。细胞阻滞在G1期。对照组和处理组p21WAF1基因表达强度分别为1．12、3．31、5．24、4．48。结论E2、TAM、RAL可以增强p21WAF1基因表达使PC3阻滞于G1期,通过下调bcl-2蛋白并上调Caspase-3蛋白诱导PC3凋亡。Objective To investigate the proliferation inhibition and apoptosis onset in human prostate carcinoma cell line PC3 induced by 17β-estradiol （E2）, tamoxifen （TAM） and raloxifene （RAL） and explore the molecular mechanism. Methods PC3 cells were exposed to different concentrations of E2, TAM and RAL for different duration. Cell apoptosis percentage and cell cycle phage distribution were measured. The expression of bcl-2, caspase-3 and P21^WAF1 mRNA was detected. Apoptotic cells were observed by hoechst staining and electron microscopy （EM）. Results A time-and dose-dependent proliferation inhibition of E2, TAM and RAL was demonstrated in PC3. Forty-eight h after treatment with 10^-4 mol/L E2, 10.5 mol/L TAM and 10^-5 mol/L RAL, apoptosis rate was （21.54± 0.91）%, （38.28 ± 1.16） % and （42.41 -± 2.26） % , respectively （ F 〈 0.05）. A G1 cell cycle arrest was induced in PC3. The expression of bcl-2 protein was decreased, while that of caspase-3 protein increased. The express/on of P21^WAF1 mRNA in PC3 （control, 10^-4 mol/L E2,10^-5 mol/L TAM and 10^-5 mol/L RAL） was 1.12,3.31,5.24,4.48,respectively. Conclusion E2,TAM and RAL could inhibit proliferation and induce apoptosis and G1 cell cycle arrest in human prostate carcinoma cell lines PC3 by increasing P21WAF1 mRNA and caspase-3 protein expression and suppressing bcl-2 protein expression.

关 键 词：前列腺癌 17Β雌二醇 他莫昔芬 雷洛昔芬 脱噬作用 

分 类 号：R737.25[医药卫生—肿瘤]