长梗秦艽酮体外抗肿瘤活性及其作用机制探讨  

Bioactivity and Mechanism Study of Waltonitone on Tumor Cells Growth in vitro

作　　者：章漳[1,2] 段朝辉[1] 丁侃[2] 王峥涛[1] 

机构地区：[1]上海中医药大学中药研究所中药标准化教育部重点实验室,上海201203 [2]中国科学院上海药物所糖生物学及糖化学实验室,上海201203

出　　处：《中国药学杂志》2010年第4期259-263,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30770484)

摘　　要：目的研究长梗秦艽酮体外抗肿瘤活性,探讨其部分作用机制。方法采用噻唑蓝(MTT)法观察长梗秦艽酮对BEL-7402,HeLa,BXPC-3,PANC-1细胞增殖的影响,流式细胞术分析其对BEL-7402细胞周期的影响,Western blot法检测其对ERK1/2蛋白激酶磷酸化的作用,RT-PCR法检测其对p53和乙酰肝素酶(heparanase)的mRNA表达水平的影响。结果长梗秦艽酮能够显著抑制4种肿瘤细胞的生长。长梗秦艽酮作用于BEL-7402细胞后能够引起S期细胞周期阻滞,激活ERK1/2磷酸化而对p38磷酸化没有影响,上调p53的mRNA表达水平,抑制乙酰肝素酶的mRNA表达。结论长梗秦艽酮具有显著的抗肿瘤活性,其作用机制可能与激活ERK1/2信号通路及上调p53基因从而诱导细胞周期阻滞和抑制乙酰肝素酶的表达有关。OBJECTIVE To investigate inhibitory effects of wahonitone （WT）, a new ursane-type pentacyclic triterpene isolated from Gentian waltonii Burkill, on several human tumor cells growth in vitro and to understand the possible mechanisms. METHODS The potential effect of WT on the cell viability was examined using MTT assay. The cell cycle distribution of BELT402 cells treated with WT was analyzed by flow eytometry. Phosphorylation of ERK1/2 and p38 MAPK were detected by Western blot, while the mRNA expression of p53 and heparanase were determined by RT-PCR analysis. RESULTS WT strongly inhibited the BELT402, HeLa, BX- PC-3, PANC-1 cells growth. WT induced S phase cell cycle arrest and activated ERK1/2 phosphorylation in BEL-7402 cells. The mRNA expression of p53 was up-regulated during WT treatment. However, the mRNA expression of heparanase was significantly decreased. CONCLUSION The anti-tumor activity of WT might be attributed partly to the induction of cell cycle arrest through ERK1/ 2 pathway and inhibition of heparanase expression by up-regulation of p53 gene.

关 键 词：长梗秦艽酮 肿瘤 细胞周期 ERK1/2 P53 乙酰肝素酶 

分 类 号：R965[医药卫生—药理学]