Proteomic Analysis of the Molecular Mechanism of Lovastatin Inhibiting the Growth of Nasopharyngeal Carcinoma Cells

Proteomic Analysis of the Molecular Mechanism of Lovastatin Inhibiting the Growth of Nasopharyngeal Carcinoma Cells
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洛伐他汀抑制鼻咽癌细胞生长分子机制的蛋白质组学分析

DOI:
10.7150/jca.30454
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发表时间:
2019-01-01
期刊:
影响因子:
3.9
通讯作者:
Guo, Can
Guo, Can
中科院分区:
医学3区
文献类型:
--
作者:
Mo, Yongzhen;Wang, Yumin;Guo, Can

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代谢异常是肿瘤的基本特征之一。越来越多的研究表明,降血脂药物洛伐他汀对肿瘤有明显的抑制作用,但在鼻咽癌方面还未见报道。本文探讨洛伐他汀对鼻咽癌细胞生长的影响及其可能的分子机制。用不同浓度的洛伐他汀处理鼻咽癌细胞后,发现洛伐他汀对鼻咽癌细胞的生长有抑制作用,并呈时间和剂量依赖性。为了探讨洛伐他汀抑制鼻咽癌生长的分子机制,我们采用LC/MS全蛋白质组学方法检测了不同时间点处理的鼻咽癌细胞的蛋白质组。利用IPA软件构建差异表达蛋白质的分子网络。研究发现,洛伐他汀主要通过影响EIF 2和mTOR信号通路抑制鼻咽癌细胞的生长,而EIF 2和mTOR信号通路调节细胞代谢和凋亡。本研究结果为进一步研究洛伐他汀抑制鼻咽癌细胞生长的分子机制提供了坚实的基础,也为洛伐他汀在鼻咽癌治疗中的临床应用提供了参考。
Metabolic abnormalities are one of the essential features of tumors. Increasingly more studies have shown that lovastatin, a lipid-reducing drug, has visible inhibitory effects on tumors, but it has not been reported in nasopharyngeal carcinoma. In this paper, we explored the effects of lovastatin on the growth of nasopharyngeal carcinoma cells and its possible molecular mechanisms. After treating nasopharyngeal carcinoma cells with different concentrations of lovastatin, we found that lovastatin can inhibit the growth of nasopharyngeal carcinoma in a time- and dose-dependent manner. To explore the molecular mechanism of how lovastatin inhibits the growth of nasopharyngeal carcinoma, we examined the proteome of nasopharyngeal carcinoma cells treated at different time points using an LC/MS whole-proteomic strategy. The molecular network of differentially expressed proteins was constructed using IPA software. It was found that lovastatin inhibited the growth of nasopharyngeal carcinoma cells mainly by affecting the EIF2 and the mTOR pathways, which regulate cell metabolism and apoptosis. The results of this study provide a robust basis for further research on the molecular mechanism of lovastatin's inhibition of nasopharyngeal carcinoma cells and provide a reference for the clinical use of lovastatin in the treatment of nasopharyngeal carcinoma.