熊果酸衍生物对人胃癌细胞的抗癌活性及凋亡诱导机制研究  

Anti-Cancer Activity of A New Ursolic Acid Derivative on Gastric Cancer Cells and the Mechanism of Apoptosis

作　　者：于舟[1] 白锴凯[1] 郭养浩[1,2] 

机构地区：[1]福州大学药物生物技术与工程研究所,福建福州350002 [2]福州大学医疗器械和药物技术重点实验室,福建福州350002

出　　处：《药物生物技术》2010年第5期382-385,共4页Pharmaceutical Biotechnology

基　　金：福建省科技厅重点实验室项目(0041815393);福建省医疗器械与医药技术重点实验室项目(200903)

摘　　要：通过对熊果酸的3位和28位进行化学修饰,制备熊果酸衍生物UA-1。采用MTT法评价熊果酸及其衍生物UA-1对不同分化程度的人胃癌细胞株AGS、BGC、MKN45的生长抑制作用,发现UA-1对3种胃癌细胞均具有较强的生长抑制作用,尤其对MKN45细胞的生长抑制作用较UA提高了近3.5倍。通过琼脂糖凝胶电泳、Annexin-V/PI双染、PI单染和流式细胞术检测UA-1对MKN45细胞的凋亡诱导作用,发现UA-1能将MKN45细胞阻断在G0/G1期,并显著诱导细胞凋亡,其作用强度呈药物浓度依赖性。进一步采用WesternBlot法检测凋亡抑制蛋白Survivin的表达,发现UA-1诱导MKN45细胞凋亡的机制可能与下调Survivin的表达有关。This work aimed to synthesize and to screen ursolic acid derivatives with prominent anti-canner activity as well as to study on its mechanisms.A new ursolic acid derivative UA-1 was prepared by chemical modification on 3 and 28 position of ursolic acid.Anti-proliferation effects of UA and UA-1 on human gastric cancer cells AGS,BGC and MKN45 were evaluated by MTT assay.UA-1 displayed a strong anti-proliferation activity on the tested cancer cells.IC50 of UA-1 for AGS,BGC and MKN45 were 16.71,23.05 and 31.51μmol/L respectively.It was notable that the growth-inhibition effect of UA-1 on MKN45 cells was increased nearly by 3.5 times compared to UA.The apoptosis effect of UA-1 on MKN45 cells was analyzed by Annexin-V/PI double staining and PI staining experiments determined by flow cytometry.The results showed that UA-1 blocked MKN45 cells in G0/G1 phase.Simultaneously,the sub-G1 peak was observed in 30～50μmol/L group of UA-1,which illustrated that UA-1 induced apoptosis on MKN45 cells in a dose-dependent manner.The expression of Survivin in MKN45 cells treated with UA-1 for 24h was down-regulated in a concentration-dependent manner.The mechanisms of apoptosis in MKN45 cells induced by UA-1 might be associated with the down-regulation of expression of Survivin.

关 键 词：熊果酸 衍生物 胃癌 人胃癌细胞株MKN45 凋亡 

分 类 号：R965[医药卫生—药理学]