摘要
近年来,紫草萘醌类衍生物因其临床应用受到副作用的限制。为寻找副作用小疗效高的新型抗肿瘤药物,合成了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮,并对其化学结构进行了鉴定。同时研究了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮对人肝癌细胞活力、凋亡的影响及其潜在机制。研究结果表明,通过MTT检测其细胞活力,发现2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮显著降低了人肝癌细胞系的细胞活力。蛋白免疫印迹结果表明,该化合物可通过上调Cle-caspase3、Bad和Bax凋亡相关蛋白表达水平来诱导肝癌细胞Hep3B凋亡。为进一步检测2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮诱导Hep3B细胞发生凋亡的原因,使用荧光探针JC-1检测了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮处理后Hep3B细胞内线粒体膜电位的变化。结果发现,与对照组相比,药物处理组线粒体膜电位显著下降,绿色荧光增强,红色荧光减弱,说明2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮能通过线粒体损伤来诱导Hep3B细胞凋亡。由于2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮显著诱导Hep3B细胞凋亡。因此,2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮具有良好的抗肿瘤活性。
In recent years,the clinical application of naphthoquinone derivatives has been limited by side effects.2-(4-methoxyphenylmercapto)-5,8-dimethoxy-naphthalene 1,4-dione was synthesized and its chemical structure was identified in order to find a new antitumor drug with few side effects and high efficacy.The effects of 2-(4-methoxy-phenylmercaptol)-5,8-dimethoxynaphthalene 1,4-dione on the viability and apoptosis of human hepatocellular carcinoma cells and its potential mechanism were studied.The results showed that 2-(4-methoxy-phenylmercapto)-5,8-dimethoxy-naphthalene 1,4-dione significantly reduced the cell viability of human hepatoma cell lines by MTT detection.Western blotting showed that the compound could induce apoptosis of Hep3B hepatoma cells by up-regulating the expression levels of Cle-caspase3,Bad and Bax apoptosis-related proteins.In order to further investigate the apoptosis of Hep3B cells induced by 2-(4-methoxy-phenylmercapto)-5,8-dimethoxy-naphthalene,4-dione,We used fluorescent probe JC-1 to detect the changes of mitochondrial membrane potential in Hep3B cells treated with 2-(4-methoxy-phenylmercapto)-5,8-dimethoxy-naphthalene,4-dione.The results showed that compared with the control group,the mitochondrial membrane potential was significantly decreased,the green fluorescence was enhanced,and the red fluorescence was weakened in the drug treatment group,indicating that 2-(4-methoxy-phenylmercapto)-5,8-dimethoxy-naphthalene,4-dione could induce apoptosis of Hep3B cells through mitochondrial damage.2-(4-methoxy-phenylmercaptol)-5,8-dimethoxy-naphthol,4-dione significantly induced apoptosis of Hep3B cells.Therefore,2-(4-methoxy-phenylmercapto)-5,8-dimethoxy-naphthalene 1,4-dione has good antitumor activity.
作者
刘晓冬
韩英浩
Liu Xiaodong;Han Yinghao(College of Life Science and Technology,Heilongjiang Bayi Agricultural University,Daqing 163319)
出处
《黑龙江八一农垦大学学报》
2024年第1期77-83,107,共8页
journal of heilongjiang bayi agricultural university
基金
黑龙江省自然科学基金项目(LH2021C061)。
