一种新型的抗癌药物可抑制增殖和上皮-间充质转化。

A novel anti-lung cancer agent inhibits proliferation and epithelial-mesenchymal transition.

机构信息

Department of Thoracic Surgery, Tongren Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

出版信息

J Int Med Res. 2022 Apr;50(4):3000605211066300. doi: 10.1177/03000605211066300.

OBJECTIVE

To synthesize a novel chalcone-1,3,4-thiadiazole hybrid and investigate its anticancer effects against NCI-H460 cells.

METHODS

()-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, 1,3-dibromopropane and 1,3,4-thiadiazole-2-thiol were used as chemical materials to synthesize compound ZW97. The NCI-H460 lung cancer cell line was selected to explore the antitumor effects of compound ZW97 and .

RESULTS

Compound ZW97 selectively inhibited cell proliferation against lung cancer cell lines NCI-H460, HCC-44 and NCI-H3122 with IC values of 0.15 μM, 2.06 μM and 1.17 μM, respectively. ZW97 suppressed migration and the epithelial-mesenchymal transition process in NCI-H460 cells in a concentration-dependent manner. Based on the kinase activity results and docking analysis, compound ZW97 is a novel tyrosine-protein kinase Met (c-Met kinase) inhibitor. It also inhibited NCI-H460 cell growth in xenograft models without obvious toxicity to normal tissues.

CONCLUSIONS

Compound ZW97 is a potential c-Met inhibitor that might be a promising agent to treat lung cancer by inhibiting the epithelial-mesenchymal transition process.

目的

合成一种新型查尔酮-1,3,4-噻二唑杂合体，并研究其对 NCI-H460 细胞的抗癌作用。

方法

（）-3-（4-溴苯基）-1-（4-羟基苯基）-2-丙烯-1-酮、1,3-二溴丙烷和 1,3,4-噻二唑-2-硫醇被用作化学原料来合成化合物 ZW97。选择 NCI-H460 肺癌细胞系来探索化合物 ZW97 对肿瘤细胞的抑制作用。

结果

化合物 ZW97 选择性地抑制肺癌细胞系 NCI-H460、HCC-44 和 NCI-H3122 的增殖，IC 值分别为 0.15 μM、2.06 μM 和 1.17 μM。ZW97 浓度依赖性地抑制 NCI-H460 细胞的迁移和上皮-间充质转化过程。基于激酶活性结果和对接分析，化合物 ZW97 是一种新型的酪氨酸蛋白激酶 Met（c-Met 激酶）抑制剂。它还抑制了异种移植模型中 NCI-H460 细胞的生长，而对正常组织没有明显的毒性。