| 刘 欢,陈宇凌,徐仁华,许嘉桐,邓海腾.SIRT3过表达通过调控细胞代谢转换抑制肾肿瘤细胞的增殖[J].,2019,19(5):801-806 |
| SIRT3过表达通过调控细胞代谢转换抑制肾肿瘤细胞的增殖 |
| SIRT3 Overexpression Inhibits Growth of Kidney Tumor Cells via Regulating Cellular Metabolic Transformation |
| 投稿时间：2018-07-08 修订日期：2018-07-30 |
| DOI：10.13241/j.cnki.pmb.2019.05.001 |
| 中文关键词: SIRT3 肾透明细胞癌 定量蛋白质组学 代谢组学 |
| 英文关键词: SIRT3 Clear cell renal cell carcinoma Quantitative proteomics Metabolomics |
| 基金项目:国家重点研究与发展计划项目（2017YFA0505103, H.T.D）；山东省医药卫生科技发展计划项目（2016WS0013, R.H.X） |
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| 中文摘要: |
| 摘要 目的：研究SIRT3对肾透明细胞癌（clear cell renal cell carcinoma, ccRCC）769-P细胞增殖和抗氧化能力的影响，并进一步探究其作用机制。方法：在769-P细胞的基础上构建SIRT3过表达稳转细胞系；利用CCK-8试剂检测769-P SIRT3过表达细胞的增殖速度；利用CellROX?Deep Red染料并结合流式细胞分析检测SIRT3过表达对769-P细胞中ROS水平的影响；利用定量蛋白质组学和代谢组学的方法，探究SIRT3对769-P细胞的作用机制。结果：CCK-8实验结果表明，769-P SIRT3过表达细胞的生长速度与对照细胞相比下降了约48%；定量蛋白质组学分析显示，769-P SIRT3过表达细胞中ALDOA、ALDOA、ENO2、PKM、LDHA、LDHB表达量下调约0.4至0.7倍，SDHB和CS上调约1.3倍；代谢组学分析显示，PEP、pyruvic acid、lactate、carnitine水平下降约0.4至0.7倍，isocitric acid和acetyl-CoA水平升高分别约1.3和2.8倍；分析还显示SIRT3过表达上调SOD2、TXN、GPX4和GLRX5的表达量约1.3至2倍，降低ROS水平约40%，增强细胞对过氧化氢的耐受力。结论：SIRT3过表达引起769-P细胞的代谢转换，从而抑制其增殖；且上调769-P细胞中抗氧化酶的表达，降低ROS水平，增强细胞的抗氧化能力。 |
| 英文摘要: |
| ABSTRACT Objective: To study the effect of SIRT3 on the proliferation and oxidation resistance of clear cell renal cell carcinoma (ccRCC) 769-P cells, and to explore its mechanism. Methods: We established SIRT3 overexpressing stable cell line in 769-P cells. The CCK-8 assay was used to measure the proliferation rate of 769-P SIRT3 OE, while flow cytometry was used to determine the level of cel- lular reactive oxygen species in 769-P SIRT3 OE cells. To explore the mechanism of SIRT3 on 769-P cells by quantitative proteomics and metabonomics. Results: CCK-8 assay showed that SIRT3 overexpression decreased cell proliferation rate. Quantitative proteomics found that SIRT3 overexpression decreased the expression of ALDOA, ALDOA, ENO2, PKM, LDHA, LDHB, which increased the ex- pression of SDHB and CS. Metabolomics found that SIRT3 overexpression decreased the level of PEP, pyruvic acid, lactate, carnitine, which increased the level of isocitric acid and acetyl-CoA. Furthermore, SIRT3 overexpression also increased the expression of SOD2, TXN, GPX4 and GLRX5, which decreased the level of cellular reactive oxygen species and enhanced resistance to oxidative stress. Conclusion: SIRT3 Overexpression inhibits growth of kidney tumor cells via regulating cellular metabolic transformation, while SIRT3 over- expression decreased the level of ROS and enhanced resistance to oxidative stress. |
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