BIBR1532 Affects Endometrial Cell Proliferation, Migration, and Invasion in Endometriosis via Telomerase Inhibition and MAPK Signaling.

IF 2 4区 医学 Q2 OBSTETRICS & GYNECOLOGY Gynecologic and Obstetric Investigation Pub Date : 2023-01-01 DOI:10.1159/000530460
Xiaoling Zhao, Dan Luo, Tingting Liu, He Zhang, Yunkai Xie, Weimin Kong
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Abstract

Objectives: The effect of telomerase inhibitor BIBR1532 on endometriotic cells was investigated to explore the inhibitory effect of targeting telomerase on endometriosis.

Design: In vitro primary cell culture study. Participants/Materials: Primary endometrial cells derived from eutopic and ectopic endometrium in patients with endometriosis.

Setting: The study was conducted in the university hospital.

Methods: Paired eutopic and ectopic endometrial cells were collected from 6 patients from January 2018 to July 2021. A TRAP assay was performed to detect the telomerase activity of the cells. MTT, cell cycle, apoptosis, migration, and invasion assays were performed to study the inhibitory effect of BIBR1532. Enrichment analysis was performed to identify the key pathways involved in endometriosis progression and telomerase action. Then, Western blotting was used to investigate the expression of related proteins.

Results: BIBR1532 treatment significantly inhibited the growth of eutopic and ectopic endometrial cells, with apoptosis and cell cycle signaling involved. Migration and invasion, important characteristics for the establishment of ectopic lesions, were also inhibited by BIBR1532. The MAPK signaling cascade, related to telomerase and endometriosis, was decreased in eutopic and ectopic endometrial stromal cells with the treatment of BIBR1532.

Limitations: The severe side effects of telomerase inhibitors might be the main obstacle to clinical application, so it is necessary to find better drug delivery methods in vivo.

Conclusions: The telomerase inhibitor BIBR1532 affects endometrial cell proliferation, migration, and invasion in endometriosis.

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BIBR1532通过端粒酶抑制和MAPK信号传导影响子宫内膜异位症的子宫内膜细胞增殖、迁移和侵袭。
目的:研究端粒酶抑制剂BIBR1532对子宫内膜异位症细胞的影响,探讨靶向端粒酶对子宫内膜异位症的抑制作用。设计:体外原代细胞培养研究。参与者/材料:子宫内膜异位症患者的原代子宫内膜细胞来源于异位和异位子宫内膜。环境:本研究在大学附属医院进行。方法:2018年1月至2021年7月收集6例患者的配对异位和异位子宫内膜细胞。采用TRAP法检测细胞端粒酶活性。通过MTT、细胞周期、凋亡、迁移和侵袭实验研究BIBR1532的抑制作用。进行富集分析以确定参与子宫内膜异位症进展和端粒酶作用的关键途径。然后用Western blotting检测相关蛋白的表达。结果:BIBR1532治疗可显著抑制异位和异位子宫内膜细胞的生长,并参与细胞凋亡和细胞周期信号传导。迁移和侵袭是异位病变形成的重要特征,BIBR1532也能抑制迁移和侵袭。与端粒酶和子宫内膜异位症相关的MAPK信号级联在异位和异位子宫内膜基质细胞中被BIBR1532治疗降低。局限性:端粒酶抑制剂严重的副作用可能是临床应用的主要障碍,因此有必要寻找更好的体内给药方法。结论:端粒酶抑制剂BIBR1532影响子宫内膜异位症患者子宫内膜细胞的增殖、迁移和侵袭。
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来源期刊
CiteScore
4.20
自引率
4.80%
发文量
44
审稿时长
6-12 weeks
期刊介绍: This journal covers the most active and promising areas of current research in gynecology and obstetrics. Invited, well-referenced reviews by noted experts keep readers in touch with the general framework and direction of international study. Original papers report selected experimental and clinical investigations in all fields related to gynecology, obstetrics and reproduction. Short communications are published to allow immediate discussion of new data. The international and interdisciplinary character of this periodical provides an avenue to less accessible sources and to worldwide research for investigators and practitioners.
期刊最新文献
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