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药学学报, 2020, 55(12): 2904-2910 |
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引用本文： |
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魏静, 冯跃平, 郑茜, 王钦, 张春. 双香豆素体外抗肿瘤活性筛选及相关机制初探[J]. 药学学报, 2020, 55(12): 2904-2910. |
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WEI Jing, FENG Yue-ping, ZHENG Xi, WANG Qin, ZHANG Chun. Anti-tumor activity screening and research on the primary mechanism of dicumarol in vitro[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2904-2910. |
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| 双香豆素体外抗肿瘤活性筛选及相关机制初探 |
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| 魏静1, 冯跃平1, 郑茜2, 王钦1, 张春1 |
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1. 西南医科大学药学院, 四川 泸州 646000;
2. 四川卫生康复职业学院, 四川 自贡 643000 |
| 摘要: |
| 为初步探讨双香豆素抗肿瘤活性及相关机制，采用CCK-8法检测双香豆素对几种肿瘤细胞株生长的影响。以HepG2为研究对象，通过对几种生理生化指标的检测初步探讨其抗肿瘤的相关机制。结果显示，双香豆素对HepG2、Hccc-9810及MDA-MB-231细胞株的生长均呈剂量和时间依赖性的抑制作用，其中HepG2对双香豆素的敏感性最高（IC50=3.19±0.68 μmol·L-1）。双香豆素可使HepG2细胞周期阻滞在S期，使Bcl-2蛋白的表达下调，cleaved caspase-9和Bax蛋白的表达升高。双香豆素可使HepG2细胞内还原型谷胱甘肽（glutathione，GSH）和超氧化物歧化酶（superoxide dismutase，SOD）含量明显降低，丙二醛（malonaldehyde，MDA）和活性氧（reactive oxygen species，ROS）水平明显升高。在低氧诱导下，双香豆素能使HepG2细胞中NAD（P）H醌氧化还原酶1[NAD（P）H quinone oxidoreductase 1，NQO1]、3-磷酸肌醇依赖性蛋白激酶1（3-phosphoinositide-dependent protein kinase 1，PDK1）及缺氧诱导因子1α（hypoxia inducible factor-1α，HIF-1α）表达量下调。上述结果表明，双香豆素可有效抑制HepG2细胞增殖，促进其周期阻滞及细胞凋亡；双香豆素可能通过抑制HepG2细胞中PDK1和NQO1的表达，导致HIF-1α下调、ROS聚集，从而产生细胞氧化应激促使HepG2细胞凋亡。 |
| 关键词:
双香豆素
HepG2
凋亡
细胞周期
氧化应激
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| Anti-tumor activity screening and research on the primary mechanism of dicumarol in vitro |
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| WEI Jing1, FENG Yue-ping1, ZHENG Xi2, WANG Qin1, ZHANG Chun1 |
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1. Department of Pharmacy, Southwest Medical University, Luzhou 646000, China;
2. Sichuan Vacotional College of Health and Rehabilitation, Zigong 643000, China |
| Abstract: |
| To study the anti-tumor activities and the related mechanisms of dicumarol, the CCK-8 method was used to identify anti-tumor activities of dicumarol. HepG2 cells were used to explore the anti-tumor mechanisms by measuring several physiological and biochemical indexes. The results show that dicumarol can significantly inhibit the growth of HepG2, Hccc-9810 and MDA-MB-231 cell lines in a dose-dependent and time-dependent manner, with HepG2 cells showing the greatest sensitivity to dicumarol (with an IC50 value of 3.19±0.68 µmol·L-1 at 48 h). Dicumarol arrested the cell cycle at S phase and down-regulated the expression of anti-apoptotic protein Bcl-2 while promoting the expression of the pro-apoptotic proteins Bax and cleaved caspase-9. Dicumarol significantly decreased the levels of glutathione (GSH) and superoxide dismutase (SOD) in HepG2 cells, and increased the levels of malonaldehyde (MDA) and reactive oxygen species (ROS). Dicumarol also down-regulated the protein levels of NAD(P)H quinone oxidoreductase 1, 3-phosphoinositide-dependent protein kinase 1, and hypoxia inducible factor-1α under hypoxic conditions. The above results show that dicumarol can inhibit the proliferation of HepG2 cells and induce cycle arrest and apoptosis. Dicumarol may down-regulate the expression of HIF-1α by inhibiting the activity of NQO1 and PDK1, which leads to the accumulation of ROS, thereby generating oxidative stress and inducing apoptosis in HepG2 cells. |
| Key words:
dicumarol
HepG2
apoptosis
cell cycle
oxidative stress
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| 收稿日期: 2020-04-21
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| DOI: 10.16438/j.0513-4870.2020-0598 |
| 基金项目: 国家自然科学基金资助项目（81001700）；四川省青年科技创新研究团队研究项目（2019JDTD0016）；泸州市-西南医科大学联合项目（2019LZXNYDJ49）. |
通讯作者: 张春,Tel:15196088137,E-mail:zc83good@126.com
Email: zc83good@126.com |
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| 作者相关文章 |
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| 魏静 在本刊中的所有文章 |
| 冯跃平 在本刊中的所有文章 |
| 郑茜 在本刊中的所有文章 |
| 王钦 在本刊中的所有文章 |
| 张春 在本刊中的所有文章 |
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