Department of Radiation Oncology, Second Affiliated Hospital, Xi'an Jiaotong University, 710004, Xi'an, China.
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, FI-00014, Helsinki, Finland.
Cell Death Dis. 2019 Feb 12;10(2):136. doi: 10.1038/s41419-019-1355-1.
Resistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell's radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.
放疗抵抗导致局部晚期食管鳞状细胞癌（ESCC）复发和治疗失败。高迁移率族蛋白 1（HMGB1）与膀胱癌和乳腺癌的放射抵抗有关。然而，HMGB1 在 ESCC 放疗反应中的作用尚未完全阐明。在这里，我们研究了 HMGB1 在 ESCC 临床样本和细胞系中对放射抵抗的作用。我们发现，HMGB1 的表达与局部晚期 ESCC 患者术后放疗后肿瘤复发有关。HMGB1 在 ESCC 细胞中的敲低导致体外和体内放射敏感性增加。在 HMGB1 抑制细胞中发现自噬水平降低，并且自噬的激活使细胞恢复了放射抵抗性。我们的结果表明，HMGB1 激活自噬，从而促进放射抵抗。HMGB1 可作为 ESCC 患者对放疗反应不良的预测因子。我们的发现还强调了 HMGB1 在 ESCC 放射增敏中的重要性。
