Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway

LIU Xin; LI Qingshan; XIE Yunpeng; ZHANG Shenglin; DONG Yi

doi:10.6039/j.issn.1001-0408.2024.02.12

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Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway

更新时间：2024-01-24

- Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway
- ZHONGGUO YAOFANG Vol. 35, Issue 2, Pages: 192-197(2024)
- 作者机构：
  
  1.承德医学院附属医院肿瘤科，河北承德　067000
  2.承德医学院附属医院神经外科，河北承德　067000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.02.12
  CLC： R965;R739.41
- Published：30 January 2024，
  
  Received：11 July 2023，
  
  Revised：01 November 2023，
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柳新,李青山,谢云鹏等.安罗替尼通过调控NF-κB信号通路对脑胶质瘤细胞恶性表型的影响 ^Δ[J].中国药房,2024,35(02):192-197.

LIU Xin,LI Qingshan,XIE Yunpeng,et al.Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway[J].ZHONGGUO YAOFANG,2024,35(02):192-197.
柳新,李青山,谢云鹏等.安罗替尼通过调控NF-κB信号通路对脑胶质瘤细胞恶性表型的影响 ^Δ[J].中国药房,2024,35(02):192-197. DOI： 10.6039/j.issn.1001-0408.2024.02.12.

LIU Xin,LI Qingshan,XIE Yunpeng,et al.Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway[J].ZHONGGUO YAOFANG,2024,35(02):192-197. DOI： 10.6039/j.issn.1001-0408.2024.02.12.

摘要

目的

探究安罗替尼通过调控核因子κB（NF-κB）信号通路对脑胶质瘤细胞恶性表型的影响。

方法

体外培养人脑胶质瘤T98G细胞，以5-氟尿嘧啶为阳性对照药物，考察不同浓度（5、10、20 μmol/L）安罗替尼对该细胞增殖、黏附、迁移、侵袭能力和上皮间质转化（EMT）相关蛋白[上皮钙黏着蛋白（E-cadherin）、神经钙黏着蛋白（N-cadherin）、波形蛋白（vimentin）、纤维连接蛋白（FN）]表达的影响，并通过加入NF-κB信号通路抑制剂（BAY 11-7082）和激活剂（prostratin）来验证安罗替尼上述作用的可能机制。

结果

5、10、20 μmol/L的安罗替尼均可显著降低细胞的增殖活力（5 μmol/L安罗替尼组除外）和迁移率，显著减少黏附细胞数和侵袭细胞数，显著上调E-cadherin蛋白的表达并下调N-cadherin、vimentin、FN蛋白的表达（

＜0.05），且20 μmol/L安罗替尼的作用与阳性对照药物相当（

＞0.05）；与10 μmol/L安罗替尼比较，通路抑制剂可使细胞增殖、黏附、迁移、侵袭能力以及N-cadherin、vimentin、FN、磷酸化NF-κB p65蛋白的表达显著降低，E-cadherin蛋白的表达显著上调（

＜0.05），而通路激活剂则可使上述指标显著逆转（

＜0.05）。

结论

安罗替尼可抑制人脑胶质瘤T98G细胞的增殖、黏附、迁移和侵袭，上述作用可能与通过抑制NF-κB信号通路进而抑制细胞EMT样进程有关。

Abstract

OBJECTIVE

To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway.

METHODS

Human glioma T98G cells were cultured

in vitro

， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF-κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib.

RESULTS

Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （

＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （

＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （

＜0.05）； above indexes were reversed significantly by pathway activator （

＜0.05）.

CONCLUSIONS

Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.

关键词

脑胶质瘤安罗替尼核因子κB信号通路上皮间质转化

Keywords

anlotinibnuclear factor-κB signaling pathwayepithelial-mesenchymal transition

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