RESUMEN
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Asunto(s)
Humanos , Bencidamina , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Fosforilación , Proliferación Celular , Línea Celular Tumoral , Apoptosis , Quinasa 2 Dependiente de la CiclinaRESUMEN
The extract 261-B_2-3 of Alternaria alternata isolated from the corn in Linxian county which is an area with high incidence of esophageal cancer induced 6-thioguanine-resistant mutants in V_(79) cells and transformation in NIH/3T3 cells. There is mutation activity in presence or absence of rat-liver-microsome prepar-ations. Treated with a range of eoncentration(32ug/ml, 64ug/ml, 128ug/ml) of the extract, high rate of transformation different from the rate treated by solvent control, is found.The results show that this extract contains direct mutagen. The high infestationincidence of Alternaria alternata in the corn of Linxian county might play an important role in the causation ofesophageal cancer in this area.