齐墩果酸抑制骨肉瘤生长的mTOR信号通路分子机制研究  

Study on mechanism of oleanolic acid in inhibiting the growth of osteosarcoma tissue by mTOR signal pathway

作　　者：周荣平[1] 贾龙梅[1] 廖小明 李晨[1] 付明福[1] 顾玉荣[1] 陈伟才[1] 何丁文[1] 程细高[1] 殷明[1] 

机构地区：[1]南昌大学第二附属医院骨科,南昌330006 [2]江西省宁都县中医院骨科,江西宁都342800

出　　处：《中华中医药杂志》2016年第4期1440-1443,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81260401);江西省卫生厅中医药课题基金项目(No.2012A046)~~

摘　　要：目的:探讨齐墩果酸(OA)通过促进凋亡、抑制mTOR信号通路从而抑制骨肉瘤生长的分子机制。方法:18只裸鼠,成功构建骨肉瘤模型后,对照组(6只)给予正常饲养;实验Ⅰ(6只)、Ⅱ组(6只)给予OA每日灌胃。观察裸鼠骨肉瘤瘤体外观形态大小变化,测量瘤体体积变化,计算抑瘤率;取瘤体组织Western blot检测凋亡蛋白Caspase-3、PARP变化情况,检测mTOR信号通路中主要蛋白p-AKT、p-S6、p-4EBP1含量变化。结果:实验Ⅰ、Ⅱ组中瘤体组织体积及重量均明显较对照组小(P<0.01);肿瘤组织中凋亡蛋白Caspase-3、PARP裂解明显比对照组中增多;瘤体组织中mTOR信号通路中主要蛋白p-AKT、p-mTOR、p-S6、p-4EBP1含量明显较对照组中减少(P<0.05)。结论:OA在体内能明显抑制瘤体生长,通过促进肿瘤细胞凋亡、抑制mTOR信号通路起作用。Objective： To explore the molecular mechanism of oleanolic acid（OA） in inhibiting the growth of osteosarcoma tissue by promoting apoptosis and inhibiting the mTOR signal pathway. Methods： Eighteen nude mice were established a osteosarcoma model, which were randomly divided into control group, treatment groupⅠ and treatment groupⅡ, with each group for 6 mice. The mice in the control group were normally maintained, while the two treatment groups were given the OA by gavage. The changes in the appearance and volume of osteogenic sarcoma tumors were observed and recorded to calculate the inhibitory rate. The proteins expression including Caspase-3, PARP, p-AKT, p-S6 and p-4EBP1 were detected with Western blot technology. Results： The volume and weight of the osteosarcoma tissue in the two treatment groups were smaller than that in the control group（P〈0.01）. Compared with the control group, the protein expression of Caspase-3 and PARP in the two treatment groups were significantly increased, the proteins expression of p-AKT, p-mTOR, p-S6, p-4EBP1, which were the key proteins in the mTOR signaling pathway, in the two treatment groups were obviously decreased（P〈0.05）. Conclusion： OA could inhibite the growth of osteosarcoma tissue in vivo, which might be related to the inhibiting effects on the osteosarcoma cells and mTOR signal pathway.

关 键 词：齐墩果酸 骨肉瘤 MTOR信号通路 

分 类 号：R285[医药卫生—中药学]