NF-κB抑制剂对前列腺癌PC-3细胞STAT3核转位的影响  

Impact of NF-κB inhibitor on STAT3 translocation in PC-3 prostate cancer cell line

作　　者：李春燕[1] 赵华新[1] 张西[1] 储黎[1] 方珏敏[1] 韩慧[1] 刘希[1] 许青[1] 

机构地区：[1]同济大学附属第十人民医院肿瘤科,上海200072

出　　处：《中华男科学杂志》2013年第6期487-494,共8页National Journal of Andrology

基　　金：国家自然科学基金(30872591)~~

摘　　要：目的:观察IL-6刺激后的前列腺癌PC-3细胞STAT3和NF-κB的表达情况;验证NF-κB抑制剂咖啡酸苯乙基酯(CAPE)对PC-3细胞IL-6和STAT3表达的影响。方法:20 ng/ml IL-6分别作用于PC-3细胞0、5、10、20、30、45 min后,Western印迹和实时荧光定量PCR检测STAT3和NF-κB蛋白和mRNA水平的表达差异;流式细胞技术检测细胞周期。采用TNF-α或TNF-α联合CAPE作用于PC-3细胞,收集培养液上清,ELISA检测IL-6的表达;同时用Western印迹检测p-STAT3的表达。结果:IL-6刺激PC-3细胞后,p-STAT3蛋白的表达明显上调,细胞增殖指数明显增高。TNF-α作用于PC-3细胞后,培养液中IL-6的表达上调,同时p-STAT3蛋白的表达亦上调(P<0.05)。CAPE联合TNF-α作用于PC-3细胞后,培养液中IL-6的表达及p-STAT3蛋白的表达均明显低于TNF-α作用后的表达水平(P<0.05)。结论:CAPE能抑制TNF-α引起的IL-6的分泌,从而抑制IL-6引起的STAT3核转位;通过CAPE抑制NF-κB表达,继而影响STAT3等相关细胞信号传导途径,可能成为前列腺癌治疗的一条新途径。Objective： To observe the changes in the expressions of STAT3 and NF-κB in PC-3 cells after IL-6 stimulation and to verify the effects of the NF-κB inhibitor caffeie acid phenethyl ester （CAPE） on the expressions of p-STAT3 and IL-6 in the PC-3 prostate cancer cell line. Methods ： PC-3 prostate cancer cells were treated with IL-6 at 20 ng/ml for 5, 10, 20, 30 and 45 min. The protein and mRNA expressions of STAT3 and NF-κB were measured by Western blot and real time PCR, respectively, and the cell cy- cle was detected by flow cytometry. The PC-3 cells were exposed to TNF-（x or TNF-α ＋ CAPE, followed by determination of the IL-6 expression in the supernatant of the cells by ELISA and the expression of p-STAT3 by Western blot. Results ： After IL-6 stimulation, both the expression of p-STAT3 protein and the proliferation index of the PC-3 cells were significantly increased, and so were the ex- pressions of IL-6 and p-STAT3 protein in the supernatant after TNF-α treatment （P 〈 0. 05 ）. TNF-α ＋ CAPE induced statistically lower expressions of IL-6 and p-STAT3 than TNF-α alone （ P 〈 0.05 ）. Conclusion ： CAPE can inhibit IL-6 secretion induced by TNF-α in PC-3 cells and thus suppress STAT3 transloeation. Therefore, by inhibiting the expression of NF-κB and affecting STAT3 and other related cell signaling pathways, CAPE may become a new therapeutie option for prostate cancer.

关 键 词：前列腺癌 PC-3细胞 白细胞介素6 肿瘤坏死因子α 信号传导子与转录活化子3 核转录因子ΚB 咖啡酸苯乙基酯 

分 类 号：R737.25[医药卫生—肿瘤]