丹参有效成分——二氢丹参酮Ⅰ抑制胃癌的作用研究

doi:10.3969/j.issn.1000-8535.2020.06.003

摘要/Abstract

摘要： 目的探讨二氢丹参酮Ⅰ在胃癌细胞中的抗癌作用。方法采用 3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法(MTT法)测定细胞活力。流式细胞术检测细胞内活性氧(ROS)水平。荧光法测定Caspase活性。裸鼠胃癌模型验证DHTS的抗癌活性。结果 MTT实验结果表明,DHTS对HCG27和AGS细胞活力具有明显的剂量依赖性和时间依赖性。在DHTS处理的HCG27和AGS细胞中,细胞内ROS水平升高,凋亡细胞增多。在DHTS处理的HCG27和AGS细胞中发现caspase-3和caspase-8活性增高,caspase-9活性不变。用N -乙酰半胱氨酸阻断ROS生成可显著逆转DHTS诱导的细胞凋亡。DHTS显著抑制小鼠肿瘤瘤体体积的增加。结论所有的研究结果都有力的说明,DHTS可以在HCG27和AGS人胃癌细胞中启动活性氧生成,诱导氧化应激和细胞凋亡,值得作为抗癌药物进一步开发。

关键词: 凋亡, 二氢丹参酮Ⅰ, 胃癌, 活性氧, 氧化应激

Abstract: Objective To evaluate the anticancer actions of dihydrotanshinone Ⅰ(DHTS)in gastric cancer cells. Methods Cell viability was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay. Intracellular reactive oxygen species (ROS)levels were determined using flow cytometry. Caspase activities were measured with fluorometric assay. The anticancer activity of DHTS in nude mouse gastric cancer model was verified. Results MTT assay showed that DHTS greatly inhibited HCG27 or AGS cell viability in dose- and time-dependent manners. Elevated intracellular ROS levels and increased apoptotic cells were observed in DHTS-treated HCG27 or AGS cells. In addition, activation of caspase-3 and caspase-8, rather than caspase-9, were noticed in DHTS-treated HCG27 or AGS cells. Furthermore, blocking ROS generation with N-acetylcysteine markedly reversed DHTS-induced cell apoptosis. DHTS inhibited the increase of tumor volume in mice. Conclusion All the findings strongly suggest that DHTS may initiate ROS generation and induce oxidative stress and cell apoptosis in HCG27 or AGS human gastric cancer cells, which deserves to be further developed as an anticancer agent.

Key words: Apoptosis, Dihydrotanshinone Ⅰ, Gastric cancer, Reactive oxygen species, Oxidative stress

钟雄东. 丹参有效成分——二氢丹参酮Ⅰ抑制胃癌的作用研究[J]. 广州医药, 2020, 51(6): 11-18.

ZHONG Xiongdong. Study on the inhibition of Salvia miltiorrhiza active ingredients, dihydrotanshinone Ⅰ, in gastric cancer[J]. Guangzhou Medical Journal, 2020, 51(6): 11-18.

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