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BET抑制剂JQ1通过下调……诱导卵巢和子宫内膜样癌细胞凋亡。

BET inhibitor JQ1 induces apoptosis of ovarian and endometrial endometrioid carcinoma cells by downregulating .

作者信息

Tanimoto Saki, Sone Kenbun, Jonouchi Yuri, Hachijo Ryuta, Suzuki Eri, Tsuboyama Natsumi, Toyohara Yusuke, Inoue Futaba, Honjoh Harunori, Fukuda Tomohiko, Taguchi Ayumi, Miyamoto Yuichiro, Iriyama Takayuki, Mori Mayuyo, Asada Ken, Komatsu Masaaki, Kaneko Syuzo, Hamamoto Ryuji, Wada-Hiraike Osamu, Oda Katsutoshi, Hirota Yasushi, Osuga Yutaka

机构信息

Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

出版信息

Oncol Lett. 2024 Dec 19;29(3):106. doi: 10.3892/ol.2024.14852. eCollection 2025 Mar.

Abstract

Although ovarian endometrioid carcinoma (OEC), frequently associated with endometrial endometrioid carcinoma (EEC), is often diagnosed at an early stage, the prognosis remains poor. The development of new, effective drugs to target these cancers is highly desirable. The bromodomain and extra-terminal domain (BET) family proteins serve a role in regulating transcription by recognizing histone acetylation, which is implicated in several types of cancer. BET inhibitors have been reported as promising cancer drugs. The present study aimed to assess the role of JQ1, a BET inhibitor, in ovarian and endometrial cancers. The sensitivity of OEC and EEC cell lines to JQ1 was assessed using cell viability and colony formation assays. Additionally, western blotting and cell cycle assays were performed to evaluate changes in c-Myc expression and apoptosis markers. Cell proliferation and colony formation assays revealed significant tumor suppression in both OEC and EEC cell lines in response to JQ1 treatment. Furthermore, treatment with JQ1 induced a decrease in expression and an increase in apoptosis markers, such as cleaved PARP and the cell population in the sub-G1 phase, in both OEC and EEC cell lines. The findings of the present study indicate that JQ1 may induce cell death through c-Myc inhibition and could be a potentially novel therapeutic agent in the treatment in OEC and EEC. However, the direct mechanism, has not been fully elucidated, warranting further investigation.

摘要

尽管卵巢子宫内膜样癌(OEC)常与子宫内膜子宫内膜样癌(EEC)相关,且常于早期被诊断出来,但其预后仍然较差。开发针对这些癌症的新型有效药物非常必要。溴结构域和额外末端结构域(BET)家族蛋白通过识别组蛋白乙酰化在调节转录中发挥作用,而组蛋白乙酰化与多种类型的癌症有关。BET抑制剂已被报道为有前景的抗癌药物。本研究旨在评估BET抑制剂JQ1在卵巢癌和子宫内膜癌中的作用。使用细胞活力和集落形成试验评估OEC和EEC细胞系对JQ1的敏感性。此外,进行蛋白质免疫印迹和细胞周期试验以评估c-Myc表达和凋亡标志物的变化。细胞增殖和集落形成试验显示,JQ1处理后,OEC和EEC细胞系均出现显著的肿瘤抑制。此外,JQ1处理导致OEC和EEC细胞系中c-Myc表达降低,凋亡标志物如裂解的PARP和亚G1期细胞群体增加。本研究结果表明,JQ1可能通过抑制c-Myc诱导细胞死亡,并且可能是治疗OEC和EEC的潜在新型治疗药物。然而,其直接机制尚未完全阐明,需要进一步研究。

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