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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
主治医师,硕士。研究方向:肿瘤学相关疾病的诊疗。E-mail:liuxin662023@163.com
副主任医师,硕士。研究方向:颅内肿瘤、脑血管病等的诊疗。E-mail:xyp830422@163.com
纸质出版日期:2024-01-30,
收稿日期:2023-07-11,
修回日期:2023-11-01,
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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.
目的
2
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
2
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
2
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(
P
<0.05),且20 μmol/L安罗替尼的作用与阳性对照药物相当(
P
>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(
P
<0.05),而通路激活剂则可使上述指标显著逆转(
P
<0.05)。
结论
2
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。
OBJECTIVE
2
To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB (NF-κB) signaling pathway.
METHODS
2
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
2
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 (
P
<0.05); the effect of 20 μmol/L anlotinib was similar to that of positive control (
P
>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 (
P
<0.05); above indexes were reversed significantly by pathway activator (
P
<0.05).
CONCLUSIONS
2
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.
脑胶质瘤安罗替尼核因子κB信号通路上皮间质转化
anlotinibnuclear factor-κB signaling pathwayepithelial-mesenchymal transition
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