Inhibition of Notch1/Hes1 signaling pathway improves radiosensitivity of colorectal cancer cells

摘要

Abstract Notch signaling pathway has been demonstrated to mediate radioresistance of several tumors. Our study aims to explore the function of Notch1/HES1 pathway in the radioresistance of colorectal cancer (CRC). The results demonstrated that expressions of Notch1 and Hes1 were up-regulated with the increasing irradiation dose. DAPT (N-[(3,5-difluorophenacetyl)acety1]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester) or si-Notch1 reduced expressions of Notch1 and Hes1, exacerbated irradiation-induced cell proliferation inhibition, and improved radiosensitivity of CRC cells. Moreover, DAPT or si-Notch1 increased radiation-induced DNA damage and attenuated radiation-triggered DNA-PK activity. Furthermore, xenograft in nude mice demonstrated that co-treated with DAPT and irradiation could inhibited tumor growth additively in vivo . Taken together, inhibition of Notch1/Hes1 signaling pathway enhances radiosensitivity of CRC cells, providing a potential therapeutic target to improve the therapeutic effect of radiotherapy for CRC patients.