Trichostatin A enhances radiosensitivity and radiation-induced DNA damage of esophageal cancer cells

Shaobo Wang; Min Song; Bo Zhang

doi:10.21037/jgo-21-560

Trichostatin A enhances radiosensitivity and radiation-induced DNA damage of esophageal cancer cells

J Gastrointest Oncol. 2021 Oct;12(5):1985-1995. doi: 10.21037/jgo-21-560.

Authors

Shaobo Wang^#¹, Min Song^#², Bo Zhang¹

Affiliations

¹ Department of Nephrology, Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
² Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

^# Contributed equally.

Abstract

Background: Trichostatin A (TSA) is emerging as a potential component of anticancer therapy. In this study, we aimed to identify the radiosensitizing effects of TSA in esophageal squamous carcinoma cell lines and identify the genomic alteration of histone acetylation associated with TSA treatment.

Methods: EC109 and KYSE450 cells were pretreated with TSA (0.1 µM) for 12 hours prior to irradiation, and the cell viability, flow cytometry, and comet assays were performed to analyze cell growth, cell apoptosis, and DNA damage, respectively. Chromatin immunoprecipitation sequencing (ChIP-Seq) was performed to identify the acetylation sites of histone H3 lysine 9 (H3K9), which was altered by TSA.

Results: Our data showed that TSA could sensitize esophageal cancer cells to radiation by inducing cell cycle arrest and increasing cell apoptosis. DNA damage induced by radiation was enhanced by TSA treatment. In addition, a total of 105 differential peak-related genes were found to be associated with TSA treatment, which was identified using ChIP-Seq with specific antibodies against acetylated histone H3K9.

Conclusions: Our data suggest that pretreatment with TSA can enhance ionizing radiation-induced DNA damage of esophageal cancer cells, which was associated with the altered histone modification of whole genome. TSA has potential implications for clinical use in increasing the anticancer efficacy of radiation.

Keywords: DNA damage; Trichostatin A (TSA); esophageal cancer cells; ionizing radiation.