Inhibitory effect of dianhydrogalactitol on DNA TopoⅡ in NCI-H460 cells
10.3969/j.issn.1001-1978.2016.11.023
- VernacularTitle:二去水卫矛醇对肺癌NCI-H460细胞DNA拓扑异构酶Ⅱ的抑制作用
- Author:
Yinmei HUANG
;
Huagang LIU
;
Guiyu SU
;
Yingjie LI
;
Xiaojie WANG
;
Xia JIANG
- Publication Type:Journal Article
- Keywords:
dianhydrogalactitol;
lung cancer;
NCI-H460 cell;
Topo Ⅱ;
Topo Ⅱ inhibitor;
molecular docking
- From:
Chinese Pharmacological Bulletin
2016;32(11):1601-1607
- CountryChina
- Language:Chinese
-
Abstract:
Aim To evaluate the antitumor activity of dianhydrogalactitol ( DAG) in vitro, and further clarify its underlying mechanisms. Methods The inhibitory effect of DAG in NCI-H460 cells was detected by CCK-8 assay and colony formation assay. The morphology of cells treated with DAG was observed under optical mi-croscope. Nuclear morphology was captured by fluores-cence microscopy after Hoechst 33342 staining. Real-time PCR was used to analyze the expression level of topoisomerase Ⅱ ( Topo Ⅱ) mRNA. The protein ex-pression level of Topo Ⅱ was detected by Western blot. Additionally, molecular docking approaches were used to predict the interaction between DAG and TopoⅡ. Results DAG exhibited potent antitumor activity in NCI-H460 cells, and inhibited cell proliferation per-sistently. DAG obviously induced nuclear morphologi-cal changes of NCI-H460 cells. Furthermore, DAG could down-regulate the mRNA and protein expression level of Topo Ⅱ detected by Real-time PCR analysis and Western blot, respectively. Molecular docking predicted that DAG could bind to Topo Ⅱ. Conclu-sion DAG can significantly inhibit the proliferation of NCI-H460 cells, and its underlying mechanisms may involve the down-regulation of Topo Ⅱ mRNA and di-rect binding to Topo Ⅱ, leading to cancer cell death.
