姜黄素对Hsp90的结合及抑制作用  

The binding and inhibition function of Curcumin to Hsp90

作　　者：王静[1] 张雅雅[1] 刘涛[1] 郭春华[1] 万幼峰[1] 

机构地区：[1]中国人民解放军第一七四医院(厦门大学附属成功医院)肿瘤科,福建厦门361001

出　　处：《现代肿瘤医学》2015年第1期32-35,共4页Journal of Modern Oncology

基　　金：南京军区医学科技创新课题资助项目(编号:11MA072)

摘　　要：目的:研究姜黄素对Hsp90的结合及抑制作用。方法:采用分子模拟对接、等温滴定微量热法及Octet技术检测姜黄素与Hsp90的结合机制。采用变性荧光素酶再复性法检测姜黄素对Hsp90的抑制作用。结果:分子模拟对接结果显示姜黄素与Hsp90的ATPase区域有特异性结合。等温滴定微量热法及Octet测定二者的结合常数分别为2.84×104L/mol和9.79×104L/mol。荧光素酶复性法确定姜黄素能通过对Hsp9 0的抑制作用阻止其对变性荧光素酶进行修复,与阳性对照GA相比(IC50值为1.14μmol/L),姜黄素对Hsp90的IC50值为7.51μmol/L。结论:姜黄素与Hsp90有较强的结合且对其分子伴侣功能具有一定的抑制效果。Objective：To study the binding and inhibition function of Curcumin on Hsp90. Methods：Molecular docking,isothermal titration calorimetry and octet assay were used to estimate the binding ability of Curcumin to Hsp90. Denatured firefly luciferase renature assay was used to confirm the inhibition function of Curcumin to Hsp90. Results：Molecular result showed that Curcumin is able to bind to the ATPase domain of Hsp90 specificly,and the binding constants were 2. 84 × 104 L/mol for isathermal titration calorimetry assayand 9. 79 × 104 L/mol for Octet assay respectively. Renaturation of firefly luciferase refolding assay further comfirmed that Curcumin can prevent Hsp90 for repairing denatured luciferase,the IC50 value was 7. 51μmol/L（ IC50 value of Geldanamycin is 1. 14μmol/L）. Con-clusion：Curcumin is able to inhibit the chaperone function of Hsp90 by the strong binding ability.

关 键 词：姜黄素 HSP90 相互作用 分子伴侣 

分 类 号：R733-61[医药卫生—肿瘤]