熊果酸抑制胶质瘤裸鼠移植瘤生长及其机制的初步探讨  

Effects of ursolic acid on proliferation of transplanted glioma in nude mice and its mechanisms

作　　者：刘琼[1,2] 叶秀峰[1,2] 张徽[2] 

机构地区：[1]重庆医科大学神经科学研究中心,重庆400016 [2]重庆医科大学基础医学院病理学教研室,重庆400016

出　　处：《第三军医大学学报》2009年第11期1041-1044,共4页Journal of Third Military Medical University

基　　金：重庆市自然科学基金(2006BB5298);重庆市教委科技研究项目基金(08032)~~

摘　　要：目的观察熊果酸对恶性胶质瘤裸鼠移植瘤细胞外信号调节激酶ERK1及核内因子C-Jun、C-Myc、Cyclin D1表达的影响,探讨熊果酸抗胶质瘤生长的机制。方法皮下注射技术复制恶性胶质瘤细胞株C6裸鼠皮下移植瘤模型,然后将其分为3组:①空白对照组,②熊果酸组(50 mg.kg-1.d-1,共20 d),③PD98059组(2 mg.kg-1.d-1,共7 d),观察处理后动物生存、移植瘤生长状况及移植瘤组织病理学形态变化;用免疫组化技术检测移植瘤组织ERK1、C-Jun、C-Myc、Cyclin D1蛋白表达变化;用原位杂交技术观察ERK1 mRNA变化。结果熊果酸组和PD98059组移植瘤生长缓慢,其肿瘤体积及质量明显低于对照组(P<0.05)。熊果酸组和PD98059组ERK1、C-Jun、C-Myc、Cyclin D1蛋白及ERK1 mRNA表达明显低于对照组(P<0.05)。结论熊果酸具有抑制恶性胶质瘤裸鼠移植瘤生长的作用,其机制可能与下调ERK1、C-Jun、C-Myc、Cyclin D1表达有关。Objective To investigate the effects of ursolic acid on the expression of extracellular signal regulated kinase （ ERK1 ）, C-Jun, C-Myc, Cyclin D1 in transplanted tumor of malignant glioblastoma cell line C6 in nude mice and the related mechanisms. Methods C6 glioblastoma cells were subcutaneously injected into nude mice to establish the subcutaneous model of glioblastoma in nude mice, and then the mouse models were divided into 3 groups： blank control group, ursolic acid group （50 mg·k^-1·d^-1, intra-abdominal injection, 20 d）, PD98059 group （2 mg·k^-1·d^-1, intra-abdominal injection, 7 d）. Survival of nude mice, growth and histopathological changes of the tumors were observed. The expressions of ERK1, C-Jun, C-Myc, and Cyclin D1 in the tumor tissues and the expression of ERK1 mRNA in the tumor tissues were detected by immunohistochemical technique （IHC） and in suit hybridization （ISH）, respectively. Results Slow growth of the implanted tumor was found in ursolic acid group and PD98059 group. The mean volume and weight of tumors in the two groups were significantly smaller than those in the blank control group （ P 〈 0. 05 ）. The expressions of ERK1, C-Jun, C-Myc, Cyclin D1, and ERK1 mRNA in ursolic acid group and PD98059 group were significantly lower than those in the control group （ P 〈 0.05 ）. Conclusion Ursolic acid can significantly inhibit the growth of the implanted glioma in nude mice through down-regulation of the expressions of ERK1, C-Jun, C-Myc, and Cyclin D1 of ERK signal transduction pathway.

关 键 词：熊果酸 移植瘤 ERK1 C—Jun C—Myc CYCLIN D1 ERK1 mRNA 

分 类 号：R284.1[医药卫生—中药学] R730.264[医药卫生—中医学]