TNXB modulates radiosensitivity of esophageal cancer through the ATM/P53 pathway

Esophageal carcinoma (ESCA) is a common malignancy, and modulating radiosensitivity is crucial for individualized treatment. Tenascin XB (TNXB) overexpression in tumors is speculated to influence radiosensitivity. This study aims to investigate whether TNXB overexpression prior to irradiation sensitizes human ESCA cells in vitro.

The expression of TNXB in tumor specimens was examined using Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The relationships between TNXB expression and clinicopathological characteristics were analyzed. Two human ESCA cell lines (TE-1 and OE33) were subjected to explore the effect of TNXB expression on radiosensitivity. DNA damage, apoptosis, cell cycle arrest, and protein expression were assessed by colony formation assay, western blotting and flow cytometry, respectively.

TNXB displayed a low expression in tumor tissues. Reduced TNXB expression was significantly correlated with larger tumor size and higher TNM stage. TNXB overexpression coupled with X-ray irradiation markedly suppressed colony formation in TE-1 and OE33 cells, and increased γH2AX expression, apoptosis rate, and promoted cell cycle arrest. Additionally, the combined treatment of TNXB overexpression and X-ray irradiation resulted in upregulation and phosphorylation of Ataxia Telangiectasia Mutated (ATM) and P53, leading to elevated cleaved-caspase3 and decreased pro-caspase3 levels. si-ATM treatment reversed these effects.

Our findings demonstrate that TNXB enhances radiosensitivity in TE-1 and TE-10 cells by the ATM/P53 pathway.