Effects of Src tyrosine kinase inhibitor dasatinib on the proliferation and apoptosis of human esophageal squamous cell carcinoma cell line KYSE180 / 肿瘤

ABSTRACT

Objective: To investigate the effects of Src tyrosine kinase inhibitor dasatinib on the cell proliferation and apoptosis of human esophageal squamous cell carcinoma and the related mechanism. Methods: Western blotting was used to detect the expressions of total Src and phos-Src tyrosine kinase in esophageal squamous-cell cancer cell lines KYSE180, EC109 and KYSE30 as well as human immortalized esophageal epithelial cell line SHEE. The inhibition effect of different concentrations of Src tyrosine kinase inhibitor dasatinib on Src kinase and the effects of dasatinib on proliferation, cell-cycle and apoptosis of KYSE180 cells as well as the growth of subcutaneous xenograft of KYSE180 cells in nude mice were examined by MTT method, flow cytometry (FCM), Western blotting and an experimental xenograft mouse model. Results: The activation level of Src tyrosine kinase was significantly increased in KYSE180, EC109 and KYSE30 cells, and this effect was not observed in SHEE cells. Dasatinib could significantly inhibit the proliferation of KYSE180 cells, and also inhibit G1/S transition, induce apoptosis and upregulate the expression levels of apoptosis-related caspase 3, cytochrome C and Bax proteins in KYSE180 cells. Furthermore, the growth of subcutaneous xenograft of KYSE180 cells in nude mice was obviously inhibited by dasatinib treatment. Conclusion: Dasatinib can inhibit the growth of subcutaneous xenograft of KYSE180 cells in nude mice by inhibiting cell proliferation, inducing apoptosis and influencing the distribution of cell cycle, and it may be considered as an effective agent for the treatment of esophageal squamous cell carcinoma. Copyright © 2012 by TUMOR.