Potent bromodomain and extraterminal domain inhibitor JAB-8263 suppresses MYC expression and exerts anti-tumor activity in colorectal cancer models
作者机构：Department of General SurgeryChinese PLA General HospitalBeijing 100039China Medical School of Chinese PLABeijing 100039China Department of ChemistryJacobio PharmaceuticalsBeijing 102600China Department of PharmacologyJacobio PharmaceuticalsBeijing 102600China Department of Anesthesiologythe Second Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300250China
出 版 物：《World Journal of Gastrointestinal Oncology》 (世界胃肠肿瘤学杂志（英文版）（电子版）)
年 卷 期：2023年第15卷第2期
页 面：332-342页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Supported by the National Natural Science Foundation of China No.81871317
主 题：Bromodomain Bromodomain and extraterminal domain inhibitor Colorectal cancer JAB-8263 MYC p21
摘 要：BACKGROUND The overexpression of the MYC gene plays an important role in the occurrence,development and evolution of colorectal cancer(CRC).Bromodomain and extraterminal domain(BET)inhibitors can decrease the function BET by recognizing acetylated lysine residues,thereby downregulating the expression of *** To investigate the inhibitory effect and mechanism of a BET inhibitor on CRC *** The effect of the BET inhibitor JAB-8263 on the proliferation of various CRC cell lines was studied by CellTiter-Glo method and colony formation *** effect of JAB-8263 on the cell cycle and apoptosis of CRC cells was studied by propidium iodide staining and Annexin V/propidium iodide flow assay,*** effect of JAB-8263 on the expression of c-MYC,p21 and p16 in CRC cells was detected by western blotting *** anti-tumor effect of JAB-8263 on CRC cells in vivo and evaluation of the safety of the compound was predicted by constructing a CRC cell animal tumor *** JAB-8263 dose-dependently suppressed CRC cell proliferation and colony formation in *** MYC signaling pathway was dose-dependently inhibited by JAB-8263 in human CRC cell ***-8263 dose-dependently induced cell cycle arrest and apoptosis in the MC38 cell ***837 xenograft model was treated with JAB-8263(0.3 mg/kg for 29 d),and the average tumor volume was significantly decreased compared to the vehicle control group(P0.001).The MC38 syngeneic murine model was treated with JAB-8263(0.2 mg/kg for 29 d),and the average tumor volume was significantly decreased compared to the vehicle control group(P=0.003).CONCLUSION BET could be a potential effective drug target for suppressing CRC growth,and the BET inhibitor JAB-8263 can effectively suppress c-MYC expression and exert anti-tumor activity in CRC models.
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