Wang Shaobo, Song Min, Zhang Bo
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.
Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Gastrointest Oncol. 2021 Oct;12(5):1985-1995. doi: 10.21037/jgo-21-560.
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.
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.
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.
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.
曲古抑菌素A（TSA）正逐渐成为抗癌治疗的一种潜在成分。在本研究中，我们旨在确定TSA对食管鳞状癌细胞系的放射增敏作用，并确定与TSA治疗相关的组蛋白乙酰化的基因组改变。
在照射前，将EC109和KYSE450细胞用TSA（0.1μM）预处理12小时，分别进行细胞活力、流式细胞术和彗星试验，以分析细胞生长、细胞凋亡和DNA损伤。进行染色质免疫沉淀测序（ChIP-Seq）以鉴定被TSA改变的组蛋白H3赖氨酸9（H3K9）的乙酰化位点。
我们的数据表明，TSA可通过诱导细胞周期停滞和增加细胞凋亡使食管癌细胞对辐射敏感。TSA处理增强了辐射诱导的DNA损伤。此外，使用针对乙酰化组蛋白H3K9的特异性抗体通过ChIP-Seq鉴定出总共105个与TSA治疗相关的差异峰相关基因。
我们的数据表明，TSA预处理可增强电离辐射诱导的食管癌细胞DNA损伤，这与全基因组组蛋白修饰的改变有关。TSA在提高放疗抗癌疗效方面具有潜在的临床应用意义。
