Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action

作者：Taofeng Zhu, Ruhua Chen, Hao Yu, Yan Feng, Jianqiang Chen, Qin Lu, Jing Xie, Weiliang Ding, Tieliang Ma · 发表于：Molecular Medicine Reports · 年份：2014 · DOI：10.3892/mmr.2014.2519 · 被引用次数：20 · 研究领域：Metal complexes synthesis and properties、Ferrocene Chemistry and Applications、Metal-Catalyzed Oxygenation Mechanisms

In order to investigate the effect of a copper (II) complexes of a coumarin derivative and phenanthroline (hereinafter referred to as the coumarin-copper drug) on lung adenocarcinoma cells in vivo and in vitro, along with the mechanism of action, LA795 lung adenocarcinoma cells were treated with different concentrations of coumarin-copper drug. An MTT assay was performed to determine the cell proliferation ratio, cell apoptosis was detected by Annexin V/propidium iodide staining with flow cytometric analysis and western blot analysis was employed to evaluate the expression levels of apoptosis-associated proteins. In addition, an LA795 cell xenograft tumor model was established in nude mice, with mice receiving intraperitoneal injection once a week for three weeks of either 2 or 4 mg/kg in three divided doses coumarin‑copper drug, or phosphate‑buffered saline. The tumor growth curves were drawn and the tumor growth inhibition rates were calculated. The apoptotic index of subcutaneously transplanted tumor cells was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end‑labeling assay. The coumarin-copper drug effectively inhibited the proliferation of LA795 cells in a dose‑ and time‑dependent manner, with the half maximal inhibitory concentration equaling 2.0 µmol/l. The coumarin-copper drug also significantly induced LA795 cell apoptosis in a time-dependent manner (P<0.05), which was accompanied by upregulation p35 and B-cell lymphoma-2 (Bcl-2)-associated X...