| 阿司匹林增加人肝癌细胞对三氧化二砷敏感性的实验研究及机制探讨 |
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| 引用本文： | 胡亚男,谷仕艳,张遵真.阿司匹林增加人肝癌细胞对三氧化二砷敏感性的实验研究及机制探讨[J].四川大学学报(医学版),2016,47(2):159-163. |
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| 作者姓名： | 胡亚男 谷仕艳 张遵真 |
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| 作者单位： | 1.四川大学华西公共卫生学院 环境卫生与职业医学系 |
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| 摘 要： | 目的 研究阿司匹林能否增加肝癌细胞对三氧化二砷（As2O3）的敏感性，并从氧化应激角度探索其增敏的机制。方法 采用10 μmol/L As2O3和不同浓度的阿司匹林联合处理人肝癌细胞HepG2 24 h后，采用MTT比色法测定细胞存活率，流式细胞术检测细胞凋亡和细胞内活性氧（ROS）水平，Western blot检测总蛋白中血红素氧合酶1（HO-1）和核蛋白中核转录因子Nrf2的表达水平。结果 与空白对照相比，10 μmol/L As2O3可引起肝癌细胞存活率降低，凋亡率、ROS水平、HO-1和Nrf2表达升高；不同浓度（0.1、1.0、2.5、5.0 mmol/L）的阿司匹林与10 μmol/L As2O3联合处理时，HepG2细胞存活率、总蛋白HO-1以及核内Nrf2的表达均随着阿司匹林浓度的增加呈现先升高后降低的趋势，而细胞凋亡率和细胞内ROS水平则表现为先降低后升高。结论 阿司匹林对As2O3的增敏作用有限，只有在较高浓度（5 mmol/L）时表现出一定的增敏作用，其增敏机制可能是通过抑制Nrf2-HO-1途径从而导致ROS蓄积，增强As2O3对HepG2的凋亡诱导能力，进而增加HepG2对As2O3的敏感性。
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| 关 键 词： | 三氧化二砷 阿司匹林 凋亡 血红素氧合酶1 核转录因子Nrf2 |
The Experiment Study and Mechanism of Aspirin Enhances Cellular Sensitivity of Hepatocellular CarcinomaCell Line to Arsenic Trioxide |
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| HU Ya-nan,GU Shi-yan,ZHANG Zun-zhenY。.The Experiment Study and Mechanism of Aspirin Enhances Cellular Sensitivity of Hepatocellular CarcinomaCell Line to Arsenic Trioxide[J].Journal of West China University of Medical Sciences,2016,47(2):159-163. |
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| Authors: | HU Ya-nan GU Shi-yan ZHANG Zun-zhenY。 |
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| Abstract: | Objective To explore whether aspirin could sensitize arsenic trioxide on human hepatocelluar carcinoma cell line and understanding the combination mechanisms underlying co-treatment. Methods Cell viability was detected by MTT assay, cell apoptosis rate and reactive oxygen species (ROS) level were measured by flow cytometry, and Western blot assay was used to estimated the protein expression of heme oxygenase-1 (HO-1) in total protein and NF-E2-related factor 2 (Nrf2) in nuclear protein. Results 10 μmol/L arsenic trioxide can decreased the cell viability, while cell apoptosis rate, ROS level, HO-1 and Nrf2 protein expression was increased ( P<0.05). When compared with arsenic trioxide alone, co-treatment of arsenic trioxide with aspirin in different concentration (0, 0.1, 1.0, 2.5, 5.0 mmol/L) exhibited dual effects in intracellular ROS level, HO-1 and Nrf2 expression. Specifically, with the increasing of aspirin concentrations, the level of ROS induced by arsenic trioxide showed a rising trend after the first reduction, whereas, HO-1 and Nrf2 protein expression were decreased at first and then increased. Conclusion Low concentration, less than 2.5 mmol/L, of aspirin may reduce the ROS accumulation through activating of Nrf2-HO-1 pathway, therefore decreasing the apoptotic cell death induced by arsenic trioxide. On the contrary, 5 mmol/L aspirin could increase the sensitivity of HepG2 to arsenic trioxide through enhancing the arsenic trioxide-induced apoptosis by ROS accumulation resulting in inhibiting the Nrf2-HO-1 pathway. |
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| Keywords: | Arsenic trioxide Aspirin Apoptosis HO-1 Nrf2 |
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