重庆医学2026，Vol.55Issue(8)：1715-1721,7.DOI:10.3969/j.issn.1671-8348.2026.08.006
安罗替尼通过抑制PI3K/Akt/ERK通路增强鼻咽癌CNE-2细胞放疗敏感性的机制研究
Mechanism study of anlotinib enhancing radiosensitivity of nasopharyngeal carcinoma CNE-2 cells by inhibiting the PI3K/Akt/ERK pathway
摘要
Abstract
Objective To investigate the effect of anlotinib on radiosensitivity of nasopharyngeal carci-noma CNE-2 cells and its potential mechanism.Methods CNE-2 cells were divided into control group,anlo-tinib group,radiotherapy group and combined group(anlotinib combined with radiotherapy).The MTT assay was used to detect the proliferative viability of CNE-2 cells treated with different concentrations of anlotinib.Western-blot was performed to determine the phosphorylation levels of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/extracellular signal-regulated kinase(ERK)pathway,the expression of apoptosis-re-lated proteins[cleaved caspase 3,myeloid cell leukemia-1(Mcl-1)]and DNA damage marker phosphorylated histone H2AX(γ-H2AX)after X-ray irradiation and anlotinib intervention.Flow cytometry was adopted to analyze cell-cycle distribution,and colony-formation assay was carried out to evaluate the radiosensitizing effect of anlotinib.Results Anlotinib inhibited the proliferation of CNE-2 cells in a concentration-and time-dependent manner(P<0.05).4 Gy irradiation significantly up-regulated the protein levels of phosphorylated(p)-PI3K,p-Akt and p-ERK(P<0.05),whereas anlotinib effectively suppressed the expression of these phosphorylated proteins(P<0.05).Compared with the control group,the proportion of cells in G2/M phase in the combined group increased by 25.7%while the proportion of S-phase cells decreased by 22.4%(P<0.05);the expression of cleaved caspase 3 was markedly elevated and Mcl-1 was obviously down-regulated(P<0.05).The γ-H2AX level in the combined group was significantly higher than that in the radiotherapy group(P<0.05).Colony-formation experiments demonstrated that the 20.0 μmol/L combination group ex-hibited the most prominent sensitization effect with the highest radiosensitization ratio(P<0.05).Conclusion Anlotinib can enhance the radiosensitivity of nasopharyngeal carcinoma cells.The underlying mechanism may involve inhibiting the PI3K/Akt/ERK signaling pathway,inducing G2/M-phase cell-cycle arrest,facilita-ting cell apoptosis and impairing the repair of DNA double-strand breaks.关键词
鼻咽癌/安罗替尼/放疗敏感性/磷酸肌醇3-激酶/蛋白激酶B通路/DNA损伤修复Key words
nasopharyngeal carcinoma/anlotinib/radiosensitivity/phosphoinositide 3 kinase/protein ki-nase B pathway/DNA damage repair分类
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赵明,秦秋子,杨艳萍,高岭..安罗替尼通过抑制PI3K/Akt/ERK通路增强鼻咽癌CNE-2细胞放疗敏感性的机制研究[J].重庆医学,2026,55(8):1715-1721,7.基金项目
河南省医学科技攻关计划项目(LHGJ20240384). （LHGJ20240384）
