盐霉素及mTOR信号通路对前列腺癌DU145干细胞的影响  

The effect of salinomycin on cancer stem cell formation of prostate cancer cell line DU145 through mTOR signaling pathway

作　　者：蒋鸿涛[1] 吴涛 章运生[1] 刘罗根[1] 蒋茂林[3] 彭潋[3] 张弘[4] 周明澍 王毅[1] 

机构地区：[1]南华大学附属第二医院,421001 [2]湖南省岳阳市第一人民医院泌尿外科,414000 [3]粤北人民医院医院泌尿外科,广东省韶关市512026 [4]南华大学第二临床学院,421001

出　　处：《实用医学杂志》2017年第13期2092-2096,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金资助(编号:81241090);衡阳市科技计划项目资助(编号:2016KJ33);南华大学"蒸湘学者"基金资助

摘　　要：目的探讨盐霉素对前列腺癌DU145干细胞的影响及其可能的机制,为盐霉素的临床应用提供理论依据。方法盐霉素处理DU145细胞,以ALDH为肿瘤干细胞标记物,用流式细胞仪检测处理后ALDH阳性的DU145干细胞的百分比。盐霉素处理DU145细胞后,用Western Blot法检测mTOR信号通路相关蛋白m-TOR、p-70s6k、p-p70s6、p-s6等的表达变化。盐霉素结合mTOR信号通路抑制剂雷帕霉素处理DU145细胞,利用流式细仪检测ALDH阳性的DU145干细胞百分比。结果盐霉素显著性抑制ALDH阳性的DU145干细胞(抑制率为77.78%),是紫杉醇的2倍(抑制率为38.64%)。盐霉素抑制mTOR信号通路相关分子m-TOR、p-70s6k、p-p70s6、p-s6等蛋白的表达,具有时间依赖性和剂量依赖性。盐霉素结合雷帕霉素能够抑制ALDH阳性的DU145干细胞比例(抑制率为77.95%)。结论盐霉素可能通过抑制mTOR通路信号来发挥抑制肿瘤干细胞的作用。Objective To investigate the effect of salinomycin on cancer stem cell formation of prostate cancer cell line DU 145 and its possible mechanisms, providing theoretical basis for the clinical application of salinomycin. Methods （1） DU145 ceils were treated with salinomycin. The percentage of ALDH＋cells, which was used as the marker of cancer stem cells, was detected by flow cytometry. （2） After treated with salmonin, DU145 cells were subjected to Western-Blot analysis for the expression of mTORsignal pathway-related proteins such as p-70s6k, p-p70s6, p-s6 and so on. 3）DU145 cells were treated with salinomycin combined with mTOR signal pathway inhibitor rapamycin, and the ALDH＋ cancer stem cells were detected using flow cytometer. Results （1） Salmonomycin significantly inhibited ALDH-positive cancer stem cells in DU145cell line （inhibition rate in 77.8% ）, which was twice as high as that of traditional anticancer drug paclitaxel （which has a inhibition rate of 38.64% ）. This results suggesting that salinomycin would have the effect of inhibiting cancer stem cells. （2）The expression ofm-TOR p-70s6k, p-p70s6 and p-s6 in mTOR signaling pathway was inhibited by salinomycin in a time-dependent and dose-dependent manner, suggesting that salinomycin would inhibite mTOR signaling pathway. （3） Salinomycin combined with rapamycin can decrease the proportion of ALDH-positive DU 145 cancer stem cells （inhibition rate in 77.95%）, suggesting that salinomycin may inhibit ALDH-positive DU145 stem cells through the mTOR signaling pathway. Conclusion Salinomycin may play an important role in inhibiting cancer stem cells by inhibiting mTOR pathway signaling.

关 键 词：盐霉素 肿瘤干细胞 乙醛脱氢酶 MTOR信号通路 

分 类 号：R737.25[医药卫生—肿瘤]