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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

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【作者】 王越; 杨洁; 高燕; 笪宇蓉; 姚智;

【Author】 WANG Yue,YANG Jie,GAO Yan,DA Yu-rong,YAO Zhi(Department of Immunology,Tianjin Medical University,Tianjin 300070,China)

【机构】 天津医科大学免疫学教研室; 天津市中心妇产科医院肿瘤科; 天津医科大学免疫学教研室 天津300070; 天津300070; 天津300052;

【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。

【Abstract】 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 lines.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 likely 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;
【Key words】 DHT; IL-6; IL-8; Ovarian carcinoma cells;
【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
  • 【文献出处】 免疫学杂志 ,Immunological Journal , 编辑部邮箱 ,2008年02期
  • 【分类号】R737.31
  • 【被引频次】4
  • 【下载频次】134
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