| 阿司匹林联合阿托伐他汀协同抑制非小细胞肺癌细胞增殖及其机制研究 |
| 投稿时间：2020-03-30 修订日期：2020-07-29 点此下载全文 |
| 引用本文：俞俊,段晶晶,张晔.阿司匹林联合阿托伐他汀协同抑制非小细胞肺癌细胞增殖及其机制研究[J].药学实践杂志,2021,39(1):38~43 |
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| 基金项目:上海交通大学附属第六人民医院南院精准医学联合研究中心第二期创新基金项目（2017B009） |
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| 中文摘要:目的 研究阿司匹林联合阿托伐他汀对非小细胞肺癌细胞A549和NCI-H460细胞增殖的影响及其作用机制。方法 采用MTS法检测阿司匹林、阿托伐他汀以及二者联合对A549和NCI-H460细胞抗增殖活性，细胞划痕实验检测A549和NCI-H460细胞的迁移和侵袭活性，Western blotting法检测NCI-H460细胞中mTOR和NFκB信号通路相关蛋白的表达，采用实时定量PCR检测NCI-H460细胞中炎症因子TNF-α和IL-1β mRNA的表达。结果 阿司匹林、阿托伐他汀单用（浓度分别≥100、5 μmol/L）以及二者联用均能明显抑制A549和NCI-H460细胞增殖和侵袭，且二者联用抑制作用大于单用。阿司匹林、阿托伐他汀以及二者联合均可以抑制NCI-H460细胞中p-NFκB、p-mTOR以及抗凋亡因子Mcl-1和Bcl-2的蛋白表达，且与单药相比，二者联合抑制作用增强。阿托伐他汀可以降低NCI-H460细胞TNF-α mRNA的表达，联合阿司匹林可以显著降低IL-1β mRNA的表达（与对照组比较下降了近50%，P<0.05）。结论 阿司匹林联合阿托伐他汀可以协同抑制非小细胞肺癌细胞A549和NCI-H460的细胞增殖，其作用机制是协同抑制了mTOR和NFκB信号通路。 |
| 中文关键词:阿司匹林 阿托伐他汀 协同作用 非小细胞肺癌 mTOR和NFκB信号通路 |
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| Study on the synergistic effects of aspirin and atorvastatin on cell proliferation of non-small cell lung cancer cells |
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| Abstract:Objective To study the synergistic effects of aspirin and atorvastatin on cell proliferation of non-small cell lung cancer cell A549 and NCI-H460 and the mechanism of these actions.Methods The proliferation of A549 and NCI-H460 cells treated by aspirin or/and atorvastatin were determined by MTS assay. The migration of A549 and NCI-H460 cells were conducted by wound-healing assay. The expression of relevant protein in mTOR and NFκB signaling pathway were detected by western blotting. The mRNA expression of TNF-α and IL-1β were detected by quantitative real-time PCR.Results Aspirin or/and atorvastatin inhibited the proliferation and migration of A549 and NCI-H460 at concentration of 100 and 5 μmol/L or greater. The effect was enhanced by the combination of aspirin and atorvastatin. Aspirin or/and atorvastatin inhibited the protein expression of the phosphorylation of mTOR and NFκB, and down-regulated anti-apoptotic regulators Bcl-2 and Mcl-1 in NCI-H460 cells. The combination treatment of aspirin and atorvastatin was more efficacious than the single treatment. Atorvastatin decreased the mRNA expression of TNF-α. The combination of atorvastatin with aspirin decreased the mRNA expression of IL-1β by nearly 50 percent compared to the control (P<0.05).Conclusion Aspirin and atorvastatin have synergistic inhibitory effects on cell growth of non-small cell lung cancer cell A549 and NCI-H460 by suppressing mTOR and NFκB signaling pathway. |
| keywords:aspirin atorvastatin synergistic effect non-small cell lung cancer mTOR and NFκB signaling pathway |
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