High-mobility group box 1 protein modulated proliferation and radioresistance in esophageal squamous cell carcinoma.

Abstract

The high-mobility group box 1 (HMGB1) protein plays an important role in a lot of biological behaviors, including DNA damage repair, gene transcription, cell replication, and cell death, and its expression is higher in many solid tumors tissues than in their adjacent normal tissues, and it is always involved in tumor proliferation, metastasis, therapeutic tolerance, and poor prognosis. However, HMGB1 in proliferation and radioresistance of esophageal squamous cell carcinoma (ESCC) remains poorly understood. In this study, the effect of HMGB1 on proliferation, cell death, DNA damage repair and radioresistance, and its underlying mechanism was investigated in human ESCC. The immunohistochemistry scores of tumor and adjacent normal tissues in ESCC tissue microarray were analyzed. Stable HMGB1 knockdown cell lines were constructed using Kyse150 and Kyse450 cells. Cell viability, radioresistance, apoptosis, autophagy, and DNA damage were determined using CCK-8, 5-ethynyl-2'-deoxyuridine, clonogenic survival assay, immunofluorescence, flow cytometry, and western blot assays. Differential analyses showed that the expression of HMGB1 in esophageal cancer tissue was significantly higher than that in adjacent normal tissues. The downregulation of HMGB1 could effectively inhibit proliferation, increase radiosensitivity, impair DNA damage repair abilities, reduce autophagy, and increase apoptosis rates in ESCC cells after irradiation. HMGB1 is expected to be a potential target for ESCC therapy and radiosensitization.