重庆医学2024,Vol.53Issue(13):1935-1940,6.DOI:10.3969/j.issn.1671-8348.2024.13.003
胶质瘤U251干细胞通过FOXO3a/β-catenin通路调控TMZ耐药性的研究
Study on glioma U251 stem cells regulate TMZ drug resistance through FOXO3a/β-catenin pathway
摘要
Abstract
Objective To explore whether or not the glioma U251 stem cell regulates its resistance to TMZ by the FOXO3a/β-catenin pathway.Methods The U251 stem cells were divided into the TMZ group(100 μmol/IL TMZ treated cells)and the control group.The Western blot and real-time quantitative reverse transcription-PCR(qRT-PCR)were used to detect the expression levels of FOXO3a,β-catenin,Nestin,CD133 and Sox2 under the TMZ action in the two groups.The stem cell pelletization experiment was used to verify the resistance of U251 stem cell on TMZ.Recombinant viral vectors pHY-FOXO3a,pHY-β-catenin-KD and PHy-β-Catenin-KD were constructed by embedding FOXO3a/β-catenin interference sequences into lentivirus pHY-LV-KD1.1 expression vector and transfected into U251 stem cells.The change of stem cell clone pellets number was measured under TMZ action.The effects of knockdown FOXO3a and β-catenin on the characteris-tics and drug resistance of U251 stem cells were observed.Results The Western blot and qRT-PCR results showed that compared with the control group,the expression levels of FOXO3a,β-catenin,Nestin,CD133 and Sox2 protein in the TMZ group were increased,the Nestin,CD133,Sox2 mRNA expression levels were in-creased(P<0.05).The clone formation experiment results showed that the majority of survival cells on 5 d after TMZ treatment were the stem cells,indicating that the U251 stem cells could better tolerate TMZ.Knoc-king down FOXO3a and β-catenin could reduce the U251 stem cell populations number,indicating that its re-sistance to TMZ was weakened.Conclusion The FOXO3a/β-catenin pathway could regulates the characteris-tics of U251 stem cell and TMZ resistance.关键词
胶质瘤/U251干细胞/FOXO3a/β-catenin/替莫唑胺/耐药性Key words
glioma/U251 stem cell/FOXO3a/β-catenin/temozolomide/drug resistance分类
医药卫生引用本文复制引用
王政,周艳玲,许可,莫菁莲..胶质瘤U251干细胞通过FOXO3a/β-catenin通路调控TMZ耐药性的研究[J].重庆医学,2024,53(13):1935-1940,6.基金项目
2021年海南省自然科学基金面上项目(821MS043). (821MS043)