Targeting RAD50 increases sensitivity to radiotherapy in colorectal cancer cells

Cheng Chen, Yuan Wang, Jing-Feng Mei, Shou-Shan Li, Hong-Xia Xu, Hua-Ping Xiong,  Xiao-Hua Wang,  Xia He

Abstract:

Radiotherapy resistance remains the major factors limiting the radiotherapy efficacy in colorectal cancer. The Mre11-RAD50-Nbs1 (MRN) complex is known to play a critical role in DNA double strand breaks (DSBs) repair pathways and thus facilitating radioresistance. Targeting MRN function can sensitize cancer cells to irradiation in some malignancies. In this study, we stably knocked down RAD50 protein in colorectal cancer (CRC) cell lines, HCT116 and DLD1, and evaluated their response to irradiation as well as the DSB repair dynamics. We observed that downregulation of RAD50 sensitized CRC cells to irradiation with reduction in DSB repair efficiency after exposure to irradiation. In addition, RAD50 was found to be upregulated in CRC cancerous tissue samples compared to non-cancerous adjacent tissues (NATs) and in patients who were resistant to RT. Elevated RAD50 expression was associated with poor patient survival in CRC. In conclusion, targeting RAD50 can serve as an efficient strategy to sensitize CRC cells to irradiation. RAD50 protein may be used as a biomarker for patient survival in CRC.