DHT对卵巢癌细胞IL-6、IL-8及其受体表达的调节作用  

Effects of DHT on the expressions of IL-6,IL-6R,IL-8,and IL-8R in ovarian carcinoma cells

作　　者：王越[1] 杨洁[1] 高燕[2] 笪宇蓉[1] 姚智[1] 

机构地区：[1]天津医科大学免疫学教研室,天津300070 [2]天津市中心妇产科医院肿瘤科,天津300052

出　　处：《免疫学杂志》2008年第2期202-207,212,共7页Immunological Journal

基　　金：国家973重大基础研究前期研究专项项目(2003CCA04300);国家自然科学基金项目(30471962,30300070)资助

摘　　要：目的初步探讨雄激素对卵巢癌细胞IL-6、IL-8及其受体表达的调节作用及作用机制。方法选择兼有雄激素受体(AR)、IL-6和IL-8及其受体表达的卵巢癌细胞系SKOV-3和OVCAR-3作为研究模型,观察5α-二氢睾酮(DHT)对IL-6、IL-8及其受体表达以及NF-κB转录的调节作用。结果DHT可促进卵巢癌细胞IL-6、IL-8分泌及相应mRNA表达,并增强IL-6基因启动子的转录活性,DHT的上述作用可被AR阻断剂氟他胺完全阻断。DHT显著提高卵巢癌细胞NF-κB亚单位p50、p65(RelA)mRNA的表达水平,其中对后者的作用与对IL-6、IL-8 mRNA的作用相平行。此外,DHT尚能调节IL-6、IL-8受体的表达。结论雄激素可能通过NF-κB信号传导途径促进卵巢癌细胞IL-6、IL-8的分泌,同时对二者受体的表达也有一定的调节作用。Objective To investigate the effects and related mechanism of androgen on the expressions of IL-6, IL-6R, IL-8, and IL- 8R in ovarian carcinoma cell hnes. Methods Human ovarian carcinoma cell lines SKOV-3 and OVCAR-3 expressing IL-6, IL-6R, IL-8, IL- 8R, and 5α-dihydrotestosterone （DHT） were selected. Effects of DHT on the expressions of IL-6, IL-6R, IL-8, and IL-8R as well as the NF- κB transcription were observed. Results DHT enhanced the secretion and mRNA expression of IL-6 and IL-8 as well as the IL-6 promoter activation in SKOV-3 cells, while the enhancement could be completely blocked by Flutamide （Flu）, an androgen receptor（AR） antagonist. Furthermore, DHT significantly promoted the mRNA levels of p50 and p65 （RelA） in SKOV-3 cells, and the effect of DHT on p65（RelA） mRNA expression was parallel with that on IL-6 and IL-8 mRNA expression. At the same time, DHT may alter the expressions of IL-6 and IL- 8 receptors in a time-dependent manner. Conclusion Androgen not only enhances IL-6 and IL-8 secretion hkely through NF-κB signal transduction pathway, but also modulates the expressions of IL-6R and IL-8R.

关 键 词：雄激素 NF-ΚB IL-6基因启动子 卵巢癌细胞 

分 类 号：R737.31[医药卫生—肿瘤]