SNG162通过上调ER-α36表达激活胶质母细胞瘤膜起始的雌激素信号通路

doi:10.11904/j.issn.1002-3070.2025.03.002

实用肿瘤学杂志 ›› 2025, Vol. 39 ›› Issue (3): 177-183.doi: 10.11904/j.issn.1002-3070.2025.03.002

SNG162通过上调ER-α36表达激活胶质母细胞瘤膜起始的雌激素信号通路

赵恩桐^1,2, 关心^1,2,3, 李洪艳^1,2, 邱韵婷^1,2, 张炳强³, 陈梦梦³, 邹伟^1,3,4, 屈超^1,2

1.辽宁师范大学生命科学学院(大连 116081);
2.辽宁师范大学生物技术与分子生物学药物研发重点实验室;
3.大连医科大学附属第一医院干细胞临床研究机构;
4.青岛瑞思德医学检验实验室有限公司

收稿日期:2024-11-04 修回日期:2025-01-19 出版日期:2025-06-28 发布日期:2025-07-02
通讯作者: 屈超,E-mail:quchao__2006@163.com
作者简介:赵恩桐,女,(2000—),硕士研究生,从事膜通道的结构与功能的研究。

SNG162 activates the estrogen signaling pathway at the membrane initiation of glioblastoma by upregulating ER-α36 expression

ZHAO Entong^1,2, GUAN Xin^1,2,3, LI Hongyan^1,2, QIU Yunting^1,2, ZHANG Bingqiang³, CHEN Mengmeng³, ZOU Wei^1,3,4, QU Chao^1,2

1. College of Life Science,Liaoning Normal University,Dalian 116081,China;
2. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery,Liaoning Normal University;
3. Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University;
4. Qingdao Re-store Life Science Co.,Ltd.

Received:2024-11-04 Revised:2025-01-19 Online:2025-06-28 Published:2025-07-02

摘要/Abstract

摘要： 目的探讨雌激素受体-α36(estrogen receptor-alpha36,ER-α36)表达变化对胶质母细胞瘤细胞U251生长的影响。方法通过免疫荧光、qRT-PCR和Western blot方法检测ER-α36和EGFR在胶质母细胞瘤细胞U87和U251中的表达和定位;通过MTT法和Western blot实验检测低浓度10^-10 mol/L的淫羊藿苷同分异构体(Icaritin,SNG162)上调ER-α36对U251细胞增殖及雌激素信号通路活性的影响。结果 ER-α36和EGFR在胶质母细胞瘤的细胞膜上共表达;与DMSO(对照组)相比,SNG162处理的U251细胞中ER-α36(P＜0.01)和EGFR表达增加(P＜0.05);进一步研究发现低浓度的SNG162增加周期相关蛋白cyclin D1、cyclin B、cyclin E和CDK4的表达(P＜0.01),提高U251细胞的增殖能力(P＜0.05)。结论低浓度的SNG162通过上调ER-α36的表达,激活雌激素介导的ERK1/2 MAPK、p38 MAPK和EGFR/Src信号通路促进胶质母细胞瘤增殖以及激活膜起始的雌激素信号通路。

关键词: 胶质母细胞瘤, 雌激素受体-α36, 雌激素, 淫羊藿苷同分异构体

Abstract: Objective The aim of this study was to explore the effects of changes in the estrogen receptor alpha 36(ER-α36)expression on the proliferation and membrane-initiated estrogen signaling in glioblastoma U251 cells. Methods The expression and localization of ER-α36 and EGFR glioblastoma U87 cells and U251 cells were determined by immunofluorescence,qRT-PCR and Western blot.The effect of upregulating ER-α 36 on U251 cell proliferation and estrogen signaling pathway activity by low concentrations of 100 pmol/L icariin isomer(SNG162)was detected by MTT assay and Western blot. Results ER-α36 and EGFR were co-expressed in the cell membrane of glioblastoma.Compared with DMSO(control group),the expression ER-α36(P＜0.01)and EGFR increased in U251 cells treated with SNG162(P＜0.05);Further experments also found that low concentrations of SNG162 increased the expression of cycle related proteins-cyclin D1,cyclin B,cyclin E and CDK4(P＜0.01),and enhanced the proliferative ability of U251 cells(P＜0.05). Conclusion The low concentration of SNG162 upregulates the expression of ER-α36,activates the estrogen-mediated ERK1/2 MAPK,p38 MAPK,and EGFR/Src signaling pathways,promotes glioblastoma proliferation,and activates the membrane initialized estrogen signaling pathway.

Key words: Glioblastomas, Estrogen receptor-alpha36, Estrogen, Icariin isomer

中图分类号:

R739.41

赵恩桐, 关心, 李洪艳, 邱韵婷, 张炳强, 陈梦梦, 邹伟, 屈超. SNG162通过上调ER-α36表达激活胶质母细胞瘤膜起始的雌激素信号通路[J]. 实用肿瘤学杂志, 2025, 39(3): 177-183.

ZHAO Entong, GUAN Xin, LI Hongyan, QIU Yunting, ZHANG Bingqiang, CHEN Mengmeng, ZOU Wei, QU Chao. SNG162 activates the estrogen signaling pathway at the membrane initiation of glioblastoma by upregulating ER-α36 expression[J]. Journal of Practical Oncology, 2025, 39(3): 177-183.

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SNG162通过上调ER-α36表达激活胶质母细胞瘤膜起始的雌激素信号通路

SNG162 activates the estrogen signaling pathway at the membrane initiation of glioblastoma by upregulating ER-α36 expression

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