Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2023; 15(2): 332-342
Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.332
Potent bromodomain and extraterminal domain inhibitor JAB-8263 suppresses MYC expression and exerts anti-tumor activity in colorectal cancer models
Xin-Mo Liu, Shao-You Xia, Wei Long, Hai-Jun Li, Gui-Qun Yang, Wen Sun, Song-Yan Li, Xiao-Hui Du
Xin-Mo Liu, Shao-You Xia, Song-Yan Li, Xiao-Hui Du, Department of General Surgery, Chinese PLA General Hospital, Beijing 100039, China
Xin-Mo Liu, Shao-You Xia, Song-Yan Li, Xiao-Hui Du, Medical School of Chinese PLA, Beijing 100039, China
Wei Long, Hai-Jun Li, Department of Chemistry, Jacobio Pharmaceuticals, Beijing 102600, China
Gui-Qun Yang, Department of Pharmacology, Jacobio Pharmaceuticals, Beijing 102600, China
Wen Sun, Department of Anesthesiology, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China
Author contributions: Liu XM performed experiments and data analysis and wrote the paper; Xia SY performed experiments; Long W and Li H collected data; Yang GQ and Sun W performed the data analysis; Du XH and Li SY designed and revised the manuscript; All authors contributed to the article and approved the submitted version.
Supported by the National Natural Science Foundation of China, No. 81871317.
Institutional animal care and use committee statement: The experimental protocols of animals in this experiment were reviewed, approved and guided by the Jacobio Animal Care and Use Management Committee.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Hui Du, MD, Chief Doctor, Deputy Director, Professor, Department of General Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100039, China. duxiaohuiplagh@sina.com
Received: November 20, 2022
Peer-review started: November 20, 2022
First decision: December 14, 2022
Revised: December 21, 2022
Accepted: December 30, 2022
Article in press: December 30, 2022
Published online: February 15, 2023
Processing time: 86 Days and 14.1 Hours
Core Tip

Core Tip: After treating colorectal cancer (CRC) cells with the bromodomain and extraterminal domain (BET) inhibitor JAB-8263, we found that MC38 cells undergo cell cycle arrest and apoptosis. In multiple human CRC cell lines, we found that JAB-8263 downregulated c-MYC expression and upregulated p21 and p16 expression, which is associated with the highly potent antiproliferative effects of JAB-8263. JAB-8263 effectively inhibited CRC growth with acceptable tolerance in tumor mouse models. Our studies suggested that BET can be a potential effective drug target for suppressing CRC growth, and JAB-8263 can effectively suppress c-MYC expression and exert anti-tumor activity in CRC models.