去甲二氢愈创木酸抑制骨肉瘤Mg63细胞生长的研究  

Nordihydroguaiaretic Acid Inhibited Growth of Osteosarcoma Mg63 Cells In Vitro

作　　者：王京亮[1] 王亮[1] 王小开[1] 张忠民[1] 金大地[1] 

机构地区：[1]南方医科大学第三附属医院脊柱外科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2012年第3期341-345,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(8151051501000024)

摘　　要：【目的】探讨去甲二氢愈创木酸对骨肉瘤细胞Mg63的生长抑制作用及其机制。【方法】应用四甲基偶氮唑蓝(MTT法)和克隆形成法测定去甲二氢愈创木酸对Mg63细胞的生长抑制作用,检测其抑制骨肉瘤细胞生长的时间效应和剂量效应;用流式细胞技术进行细胞周期分析;用Western blot法检测药物对Mg63细胞mTORC1信号通路活性的影响。【结果】去甲二氢愈创木酸对Mg63细胞具有明显的生长抑制作用,且呈时间依赖和剂量依赖关系,72 h IC50值为(48±2)μmol/L。10、20、50μmol/L可显著抑制Mg63克隆形成数量,且随剂量增加抑制作用明显增强。细胞周期阻滞于G0/G1期,mTORC1信号通路蛋白p-S6和p-4E-BP1与对照组相比明显下调。【结论】去甲二氢愈创木酸明显抑制骨肉瘤细胞mg63增殖,诱导细胞周期阻滞于G0/G1期,这一作用可能是通过对mTORC1信号通路的抑制完成。[ Objective ] To study the growth inhibitory effects and its potential molecular mechanism of nordihydroguaiaretic acid on human osteosarcoma Mg63 ceils. [ Methods ] Effects of nordihydroguaiaretic acid on proliferation, cell cycle progression in osteosarcoma Mg63 ceils, and involvement of mTORC1 signaling in this process were examined by MTr assay, colony formation assay, flow cytometry, and Western blot analysis. [ Results] Nordihydroguaiaretic acid inhibited Mg63 cell proliferation, colony formation dose and time-dependently, induced GO/G1 arrest in osteosarcoma MG63 cells. The 72 h ICS0 value of nordihydroguaiaretic acid for Mg63 was （48 ±2） μmol/L. 10, 20, and 50 μmol/L nordihydroguaiaretic acid inhibited the colony formation obviously. The protein level of downstream target of mTORC1 phosphorylation of S6 and 4E-BP1 was down-regulated. [Conclusion] Nordihydroguaiaretic acid is a promising agent for treatment of osteosarcoma and mTORC1 signaling may contribute to its growth inhibitory effects on osteosarcoma cells.

关 键 词：骨肉瘤 去甲二氢愈创木酸 增殖 mTORC1 

分 类 号：R738.1[医药卫生—肿瘤]