Neoplasma. 2018;65(1):75-80. doi: 10.4149/neo_2018_170219N128.
Radiotherapy resistance remains the major factor limiting the radiotherapy efficacy in colorectal cancer. The Mre11-RAD50-Nbs1 (MRN) complex is known to play a critical role in the DNA double strand breaks (DSBs) repair pathways and thus facilitates 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.
放疗抵抗仍然是限制结直肠癌放疗疗效的主要因素。Mre11-RAD50-Nbs1（MRN）复合物在 DNA 双链断裂（DSBs）修复途径中起着关键作用，从而促进了放疗抵抗。靶向 MRN 功能可以使一些恶性肿瘤中的癌细胞对辐射敏感。在这项研究中，我们在结直肠癌细胞系 HCT116 和 DLD1 中稳定敲低 RAD50 蛋白，并评估它们对辐射的反应以及 DSB 修复动力学。我们观察到 RAD50 的下调使 CRC 细胞对辐射敏感，辐射后 DSB 修复效率降低。此外，与非癌相邻组织（NAT）和对 RT 有抵抗性的患者相比，CRC 癌组织样本中 RAD50 的表达上调。RAD50 的高表达与 CRC 患者的不良生存相关。总之，靶向 RAD50 可以作为一种有效的策略来使 CRC 细胞对辐射敏感。RAD50 蛋白可作为 CRC 患者生存的标志物。
