山酮类化合物抑制人脑胶质瘤细胞增殖活性及作用机制探讨  

Study on anti-growth activity and its mechanism in glioma cells by xanthones

作　　者：韩懿岚[1] 王思明[2] 李晓峰[1] 董玫[1] 路新华[2,3] 史清文[2] 丛斌[1] 谷建平[1] 

机构地区：[1]河北医科大学法医学系,河北石家庄050017 [2]河北医科大学药学院,天然药物化学教研室,河北石家庄050017 [3]华北制药集团新药研究开发有限责任公司微生物药物国家工程研究中心,河北石家庄050015

出　　处：《中国药理学通报》2011年第9期1227-1230,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81072551);河北省自然科学基金资助项目(NoC2010000489);河北省科技支撑资助项目(No11276103D-89)

摘　　要：目的检测3种山酮类化合物对人脑肿瘤细胞(T-98、U251SP和KT)增殖的抑制作用,并进一步探讨其可能的作用机制。方法研究从3种微生物次生代谢产物中纯化的山酮类化合物对人脑肿瘤细胞增殖的抑制作用。MTT比色法检测细胞增殖抑制率;利用双荧光素酶报告基因检测系统检测p53和Bax报告基因的表达;采用Western blot分析与凋亡相关的蛋白表达变化。结果 Austocystin H对KT细胞的增殖显示极强的抑制活性,呈剂量依赖性,IC50仅为0.69μmol.L-1;Austocystin H可诱导KT细胞内Bax报告基因表达(P<0.01);Western blot分析结果显示由Austocystin H处理的KT细胞中的p53和Bax的表达与对照组相比增加(P<0.05)。结论 Austocystin H具有极强的抑制人脑肿瘤细胞增殖作用,其作用机制可能与其诱导肿瘤细胞凋亡有关。Aim To discover the anticancer effect of three xanthones and to study its mechanisms. Methods Anticancer xanthone compounds from microbial metaboites were screened by measuring the antiproliferation effects on human glioma cell lines. The cell via- bilities were examined by MTY assay. KT cells were transiently cotransfeeted by pG53-Luc, pGBax-Luc reporter plasmid and SV-40-Rluc plasmid. The effects of Austoeystin H of luciferase activity expression were de- tected by Dual-Luciferase Reporter Assays. The protein expression of apoptosis in KT cells was analyzed by Western blot assay. Results Austocystin H exhibitedsignificant inhibitory effects on KT cells, and ICso value of KT cell was 0. 69 μmol · L-1 exposure. The re- porter gene of Bax was observed in response to Austocystin H. Austocystin H also up-regulated the p53 and Bax protein expression in KT cells. Conclusions Au- stocystin H has a significant inhibitory effects on human gliome cells. The possible mechanism of the inhibitory effects of Austocystin H is through inducing cell apoptosis.

关 键 词：山酮 Austocystin H 脑肿瘤细胞 增殖 报告基因 细 胞凋亡 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]