Effects and underlying mechanisms of homologous recombina-tion-associated protein XRCC3 on esophageal squamous-cell carci-noma radiotherapy response / 中国肿瘤临床

ABSTRACT

Objective:To investigate the effects and underlying mechanisms of XRCC3 on esophageal squamous-cell carcinoma (ESCC) radiotherapy response. Methods:Expression levels of XRCC3 were detected by reverse transcription PCR, Western blot, and immunohistochemistry. We knocked down XRCC3 with lentiviral infection in ESCC cells. Cell apoptosis was examined by flow cytom-etry. DNA damage and telomere dysfunction-induced foci were determined by immunofluorescence. Results:The expression levels of XRCC3 in ESCC cells and tissues were higher than those in normal esophageal epithelial cells and corresponding adjacent noncancer-ous esophageal tissues. Knockdown of XRCC3 in ESCC cells substantially increased the therapeutic efficacy of radiation. We demon-strated that the radiation resistance of XRCC3 was attributed to the XRCC3-maintaining telomere stability, which reduced ESCC cell death through radiation-induced apoptosis. Conclusion: Our data suggested that XRCC3 protects ESCC cells from ionizing radia-tion-induced DNA damage and death by enhancing telomere stability. Thus, XRCC3 can be used as a promising therapeutic target for ESCCs.