呋喃二烯抑制脑胶质瘤作用  

Experimental research on the inhibitory effect of furanodiene on glioblastoma

作　　者：杜丽媛[1] 陈燕[1] 宋荣霞[1] 林东海[1] 孙秀燕[1] 

机构地区：[1]烟台大学药学院,山东烟台264005

出　　处：《沈阳药科大学学报》2013年第4期292-297,共6页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(30973949);山东省自然科学资助基金(ZR2009CM)

摘　　要：目的观察呋喃二烯(furanodiene,FDE)纳米乳对颅内移植G422胶质母细胞瘤小鼠化疗后的生存期变化及病理改变,并初步探讨其作用机制,评估FDE纳米乳对胶质母细胞瘤的抑制作用。方法将G422胶质母细胞瘤细胞植入昆明小鼠脑白质中建模,考察FDE纳米乳及其与卡莫司汀联合组对荷瘤小鼠生存期的影响,观察各组瘤组织的病理结构变化。采用细胞增殖抑制法、Hoechst33258染色法和Annexin V-FITC/PI双染法流式细胞术检测细胞凋亡率等方法初步探索FDE对人胶质瘤U251细胞的作用机制。结果 FDE纳米乳(80 mg·kg^(-1))组治疗荷瘤小鼠生命延长率为28.1%,联合组生命延长率可达69.0%;组织病理学分析显示,FDE纳米乳组肿瘤细胞排列疏松,未见明显侵润;联合组肿瘤体积小,且与周围组织间边界清晰。细胞增殖抑制和Hoechst33258荧光染色实验均表明FDE对U251细胞增殖抑制具有浓度依赖性,流式细胞术结果分析当FDE浓度为18.5μmol·L^(-1)时,U251细胞早期凋亡率可达71.8%。结论 FDE通过调节胶质母细胞的增殖、早期凋亡等机制,有效抑制小鼠胶质瘤的生长。Objective To observe the change of survival periods and tumor pathology of G422 glioma mice treated by furanodiene （FDE） nanoemulsion, explore its mechanism and evaluate the therapeutic potential of FDE nanoemulsion using G422 glioblastoma model. Methods G422 glioblastoma cells were implanted into white matters of KM mice. The survival periods of the mice were measured and pathology of glioma in all the groups were investigated. Inhibitory effects and mechanism of FDE on proliferation of human malignant glioma U251 cells werestudied by MTT assay, Hoechst 33258 fluorescence staining and flow cytometry. Re- sults The mice treated with FDE nanoemulsion had significantly longer survival periods compared with those of the mice in the control group. The survival periods of the mice in the FDE nanoemulsion group and the combination group were 28. 1% and 69. 0% longer than those of control group, respectively. Histological pathological examination showed that the tumor cells in the mice treated with FDE nanoemulsion had loose arrangement and unclear invasion. The tumor of the mice in the combination group had clear boundary with normal tissues and was smaller than those in the other groups. The results of MTT and Hoechst 33258 fluo- rescence staining showed that dose-response relationship was exhibited between FDE and the inhibitory effects on U251 cells. In addition, the analysis of flow cytometry showed the early apoptosis rate of U251 cells in the mice treated by FDE （ 18.5 μmol. L-1 ） was 71.8%. Conclusions The FDE can inhibit the growth of G422 mice glioblastoma via the mechanism of proliferation and early apoptosis of glioblastoma ceils.

关 键 词：呋喃二烯 呋喃二烯纳米乳 胶质母细胞瘤 颅内模型 

分 类 号：R73[医药卫生—肿瘤] R96[医药卫生—临床医学]