山楂酸通过PI3K/Akt/mTOR通路诱导鼻咽癌CNE2细胞自噬研究

Maslinic acid induces autophagy through PI3K/Akt/mTOR pathway in human nasopharyngeal carcinoma cells

目的研究山楂酸对鼻咽癌CNE2细胞增殖和自噬的影响,探讨PI3K/Akt/mTOR通路在该过程中的调控作用。方法采用CCK-8法检测不同浓度的山楂酸作用不同时间对CNE2细胞增殖的影响;MDC染色法检测不同浓度山楂酸处理CNE2细胞24 h后自噬小体的形成情况;Western blotting法检测山楂酸对CNE2细胞自噬相关蛋白及PI3K/AKT/mTOR通路关键蛋白表达的影响。结果与溶剂对照组相比,山楂酸可以抑制CNE2细胞的增殖,而且随药物处理时间和浓度的增加,抑制效果增强(P<0.05);山楂酸能够诱导细胞自噬小体的形成,且可显著提高Atg5和LC3-II/LC3-I的表达,降低p62的表达;此外,山楂酸可抑制PI3K-p110α、p-Akt和p-mTOR的蛋白表达。结论山楂酸可抑制鼻咽癌细胞增殖,诱导鼻咽癌细胞发生自噬,其机制与PI3K/Akt/mTOR信号通路有关,可作为治疗鼻咽癌的潜在药物研究。

Objective To investigate the effects of maslinic acid(MA)on the proliferation and autophagy in nasopharyngeal carcinoma CNE2 cells and to elucidate the regulatory role of PI3K/Akt/mTOR pathway in this process.Methods The effect of MA on the proliferation of CNE2 cells was assessed by CCK-8.MDC staining of autophagic vacuoles was performed for autophagy analysis.Additionally,the levels of autophagy-and PI3K/Akt/mTOR-associated proteins were examined using western blot analysis.Results MA significantly inhibited the proliferation of CNE2 cells in a dose-and time-dependent manner.MA displayed autophagy-inducing effect,as shown by the increased MDC-labeled vacuoles,up-regulated LC3-II/LC3-I ratio and Atg5,as well as the down-regulated p62 level after MA treatment.Moreover,we observed that MA inhibited the expression of PI3K-p110αand the phosphorylation of Akt and m TOR.Conclusion MA inhibits the proliferation and induces the autophagy of CNE2 cells,the mechanism may be related to the PI3K/Akt/mTOR signaling pathway.These results imply that MA may be a potential anti-cancer agent for use in the treatment of nasopharyngeal carcinoma.