医学临床研究
  2025年6月3日 星期二           首 页    |    期刊简介    |    编委会    |    投稿指南    |    期刊订阅    |    广告合作    |    留言板    |    联系我们    |    English
医学临床研究  2024, Vol. 41 Issue (5): 688-692    DOI: 10.3969/j.issn.1671-7171.2024.05.013
  论著 本期目录 | 过刊浏览 | 高级检索 |
N-钙黏蛋白与Wnt/β-catenin通路在骨髓间充质干细胞与白血病干细胞中的耐药机制研究*
马小美, 吴爱瑜, 邓嘉仪, 吴维颢, 陈隆天, 黄建清, 余莲**
福建省龙岩市第一医院血液风湿科,福建 龙岩 364000
The Molecular Mechanisms of the N-cadherin and the Wnt/β-catenin Pathway Facilitate Drug Resistance in Leukemia Stem Cells and Mesenchymal Stem Cells
MA Xiaomei, WU Aiyu, DENG Jiayi, et al
Longyan First Hospital Affiliated to Fujian Medicine University, Longyan Fujian 364000
全文: PDF (1900 KB)   HTML (1 KB) 
输出: BibTeX | EndNote (RIS)      
摘要 【目的】探讨N-钙黏蛋白(N-cadherin)与Wnt/β-catenin通路在骨髓间充质干细胞(MSC)与白血病干细胞(LSC)中的耐药机制研究。【方法】65例急性髓系白血病(AML)患者,完全缓解41例,未缓解24例,比较两组CD34+CD38-干细胞中N-cadherin的表达差异。根据不同MSC或去甲氧柔红霉素(IDA)处理下将CD34+CD38- Kg1α细胞分为6组,检测细胞增殖和凋亡情况及N-cadherin、β-catenin水平,检测细胞黏附及抗凋亡能力。【结果】未缓解患者的N-cadherin表达水平高于完全缓解者(P<0.01);LSC+IDA组(B组)细胞凋亡率显著高于LSC与MSC直接共培养+IDA组(D组)(P<0.05);在IDA浓度为100 nmol/L、200 nmol/L时, B组的细胞增殖抑制率显著高于D组(P<0.05);B 组的集落形成率显著低于D组(P<0.05)。Western blot结果显示:N-cadherin及β-catenin在MSC直接接触培养条件下表达高于单独培养或分离培养;LSC在MSC共培养条件下,N-cadherin及β-catenin表达水平上升,伴随细胞核内β-catenin水平上升。【结论】骨髓微环境的MSC可以通过N-cadherin与LSC的黏附作用支持LSC的增殖能力,同时促进LSC Wnt/β-catenin通路的激活,对化疗药物产生耐药性。
服务
把本文推荐给朋友
加入我的书架
加入引用管理器
E-mail Alert
RSS
作者相关文章
关键词 白血病,髓样,急性钙结合蛋白质类抗药性,肿瘤    
Abstract:【Objective】To explore the molecular mechanisms of the N-cadherin and the Wnt/β-catenin pathway facilitate drug resistance in leukemia stem cells (LSC) and mesenchymal stem cells (MSC).【Methods】The study included 65 patients with acute myeloid leukemia (AML), of whom 41 achieved complete remission (CR group) and 24 did not (non-remission, NR group). The expression of N-cadherin in CD34+CD38- stem cells was compared between these two groups. The CD34+CD38- Kg1α cells were further divided into six groups based on different treatments with MSC or idarubicin (IDA) that cell proliferation, apoptosis, and levels of N-cadherin and β-catenin were assessed. The cell adhesion and anti-apoptotic capabilities were also evaluated.【Results】The N-cadherin expression in the NR group compared was significantly higher than that in the CR group (P<0.01).The apoptosis rate in the LSC+IDA group (Group B) was significantly higher than that in the LSC and MSC co-culture + IDA group (Group D) (P<0.05). At IDA concentrations of 100 and 200 nmol/L, the proliferation inhibition rate in Group B was significantly higher than that in Group D (P<0.05). The colony formation rate in Group B was significantly lower than that in Group D (P<0.05). The Western blot results showed that the expression levels of both N-cadherin and β-catenin were higher in direct co-culture condition of MSC than in solo cultures or non-contact co-cultures. In co-culture condition with MSC, LSC showed increased expression levels of N-cadherin and β-catenin, along with an increase in nuclear β-catenin level.【Conclusion】MSCs in the bone marrow microenvironment can support the proliferation of LSC through N-cadherin-mediated adhesion and promote the activation of the Wnt/β-catenin pathway in LSC, thereby enabling them to evade the cytotoxic effects of chemotherapy.
Key wordsLeukemia, Myeloid, Acute    Calcium-Binding Proteins    Drug Resistance, Neoplasm
收稿日期: 2024-01-27     
中图分类号:  R733.72  
基金资助:*龙岩市科技计划项目(2020LYF17028)
通讯作者: **E-mail:yulian-ly@126.com   
引用本文:   
马小美, 吴爱瑜, 邓嘉仪, 吴维颢, 陈隆天, 黄建清, 余莲. N-钙黏蛋白与Wnt/β-catenin通路在骨髓间充质干细胞与白血病干细胞中的耐药机制研究*[J]. 医学临床研究, 2024, 41(5): 688-692.
MA Xiaomei, WU Aiyu, DENG Jiayi, et al. The Molecular Mechanisms of the N-cadherin and the Wnt/β-catenin Pathway Facilitate Drug Resistance in Leukemia Stem Cells and Mesenchymal Stem Cells. JOURNAL OF CLINICAL RESEARCH, 2024, 41(5): 688-692.
链接本文:  
http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2024.05.013     或     http://journal07.magtech.org.cn/yxlcyj/CN/Y2024/V41/I5/688
版权所有 © 2013 医学临床研究杂志社  湘ICP备13012052号-1
办公地址:湖南省长沙市芙蓉区新军路43号煤炭大院主办公楼6楼621、623、632、636室 邮编:410011 电话(传真):0731-84824007 E-mail:jcr_cs.hn@vip.163.com
技术支持:北京玛格泰克科技发展有限公司 技术支持:support@magtech.com.cn