mPGES-1对激素非依赖性前列腺癌细胞Beclin-1表达的影响及其意义  

Effect of mPGES-1 on expression of Bedin-1 in androgen dependent prostate cancer cells

作　　者：钱铭[1] 许露伟[1] 许衍超[1] 吴剑平[1] 李文成[1] 贾瑞鹏[1] 

机构地区：[1]南京医科大学附属南京第一医院泌尿外科,210006

出　　处：《中华实验外科杂志》2011年第12期2040-2042,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察膜结合型前列腺素E2合成酶1（mPGES-1）对激素非依赖性前列腺癌（AIPC）细胞DU-145中自噬基因Beelin-1表达的影响。方法进行DU-145细胞培养，分别采用不同浓度（0、1、10、20、50umol／L）的特异性mPGES-1抑制剂CAY10526对DU-145细胞进行干预，通过噻唑蓝（MTr）实验，观察CAY10526对DU-145细胞增殖（A值）的影响并确定CAY10526的最佳作用浓度；Westernblot检测CAY10526干预后的DU-145细胞中Beclin—1蛋白表达。结果经不同浓度（0、1、10、20、50umol／L）的CAY10526干预12h后，Du-145细胞增殖活性（A值）依次为0．41±0．18、0．34±0．08、0．22±0．04、0．08±0．02、0．06±0．01，其中，10、20和50umoL／L组的细胞活性较空白组均有显著降低（P〈0．05），并具有剂量依赖性特征；mPGES-1在CAY10526（10、20umoL／L）干预后的蛋白表达量显著降低（P〈0．05），无血清组以及采用CAY10526（10umol／L）部分阻断mPGES-1后，Beelin-1表达均显著上调（P〈0．05），当癌细胞几乎失去活性时，mPGES-1和Beelin-1表达则同时下调（P〈0．05）。结论mPGES—1对AIPC细胞中Beclin-1介导的自噬可产生重要作用，阻断mPGES—1可上调Beelin-1表达，促进AIPC细胞死亡，提示mPGES-1可能成为治疗AIPC的新靶点。Objective To investigate the effect of microsomal prostaglandin synthase-1 （mPGES-I） on the expression of Beclin-1 in androgen independent prostate cancer （AIPC） cell line DU-145 cells. Methods DU-145 cells were treated with various concentrations （0, 1, 10, 20, 50 umol/L） of CAY10526 （specific mPGES-1 inhibitor）. The cell viability was measured by methyl thiazol tetrazolium （MTT） assay （A value） and the best working concentration of the mPGES-1 inhibitor （CAY10526） was ascertained. The effect of CAY10526 treatments on the expression of Beclin-1 in DU-145 cells was studied by using Western blotting. Results After treatment with different concentrations （0, 1, 10, 20, 50 p, mol/ L） of CAY10526 for 12 h, the cytoactive of DU-145 cells （A value） was 0. 41 ±0. 18, 0. 34 ±0. 08, 0. 22 ± 0. 04, 0. 08 ± 0. 02, 0. 06 ± 0. 01, respectively. The growth of DU-145 cells and the expression of mPG- ES-1 were suppressed significantly by CAY10526 （P 〈 O. 05 ） in a does-dependent manner. Inhibiting mPGES-1 by CAY10526 in 10 umol/L could up-regulate the expression of Beclin-1 significantly （P 〈 0.05 ）. When almost DU-145 cells were dead, both mPGES-1 and Beclin-1 were down-regulated significantly （ P 〈 0. 05 ）. Conclusion MPGES-1 plays an important role in autophagy mediated by Beclin-1 in AIPC cell lines. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1, suggesting that inhibition of mPGES-1 may be therapeutically useful in the treatment and prevention of AIPC in the future.

关 键 词：前列腺素E2合成酶 BECLIN-1 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤]