RESUMEN
Lung cancer has been one of the most common malignancies in the world. Cell senescence has been recognized as the avenue to inhibit tumor progression. However, the mechanisms remain poorly understood. In the present study, we have shown that synaptotagmin-7 (SYT7) expression was up-regulated in lung cancer. SYT7 also promoted the growth and colony formation of lung cancer cells and inhibited their senescence. In a molecular mechanism study, SYT7 was shown to interact with P53 and to potentiate the interaction between P53 and MDM2. Taken together, the present study demonstrates the oncogenic roles of SYT7 in lung cancer, and suggests that SYT7 may be a good therapeutic target for lung cancer treatment.
Asunto(s)
Neoplasias Pulmonares/patología , Sinaptotagminas/metabolismo , Células A549 , Línea Celular Tumoral , Senescencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Sinaptotagminas/genética , Ensayo de Tumor de Célula Madre , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1.24). In vivo tumor growth of xenografts was inhibited markedly by irradiation (IR) combined with ART, with a tumor inhibition rate of 53.76% in IR + ART group vs. 41.13% in IR-alone group. Pretreatment with ART significantly prompted cell apoptosis and reversed the IR-induced G2/M arrest. ART treatment could aggravate DNA damage of EC cells and prolong the formation of γ-H2AX foci induced by IR. ART up-regulated P21 and down-regulated the expression of cyclin D1, RAD51, RAD54, Ku70 and Ku86 protein of irradiated TE-1 cells. These findings support that ART induce radiosensitivity of TE-1 cells in vitro and in vivo, and may prove to be a promising radiosensitizer for EC treatment.