Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway

作者全名："Xia, Wei-Feng; Zheng, Xiao-Li; Liu, Wen-Yi; Huang, Yu-Tang; Wen, Chun-Jie; Zhou, Hong-Hao; Wu, Qing-Chen; Wu, Lan-Xiang"

作者地址："[Xia, Wei-Feng; Wu, Qing-Chen] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China; [Zheng, Xiao-Li; Liu, Wen-Yi; Huang, Yu-Tang; Wen, Chun-Jie; Wu, Lan-Xiang] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Zhou, Hong-Hao] Cent South Univ, Pharmacogenet Res Inst, Inst Clin Pharmacol, Changsha 410078, Peoples R China"

通信作者："Wu, QC (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China.; Wu, LX (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China."

来源：CANCER GENE THERAPY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001184665600001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy."

基金机构："Natural Science Foundation of China [82073938, 82274023, 82373135]; Youth Innovation in Future Medicine, Chongqing Medical University [W0093]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202200432]"

基金资助正文："This work was supported by the Natural Science Foundation of China (No. 82073938, 82274023, 82373135), Youth Innovation in Future Medicine, Chongqing Medical University (No. W0093), and the Scientific and Technological Research Program of Chongqing Municipal Education Commission (No. KJQN202200432)."