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.