摘要
研究Antimycin类天然产物对三阴性乳腺癌细胞MDA⁃MB⁃231特异性生长抑制和杀伤作用.三种结构类似的天然产物Antimycin⁃1,⁃2和⁃3对MDA⁃MB⁃231细胞生长都有很强的抑制作用,其IC50分别为1.34±0.07,160±20和180±50 nmol·L^(-1),Antimycin⁃1活性是Antimycin⁃2和Antimycin⁃3的一百多倍.10 nmol·L^(-1)的Antimycin⁃1就可有效抑制MDA⁃MB⁃231细胞增殖,药物处理细胞24和48 h后的抑制率分别达到约80%和90%.显微镜下可以观察到,10和100 nmol·L^(-1)的Antimycin⁃1都不同程度地杀伤MDA⁃MB⁃231细胞,1000 nmol·L^(-1)的Antimycin⁃1甚至使细胞几乎消溶,只留下突起的核和胞质残骸.而同样浓度药物造成的乳腺正常细胞MCF⁃10A和结肠癌细胞HCT116形态的改变不明显.1和5 nmol·L^(-1)的Antimycin⁃1对细胞集落抑制率分别达到52%和95%.20和50 nmol·L^(-1)的Antimycin⁃1也明显改变MDA⁃MB⁃231细胞核形态,核呈畸形,皱缩严重,核膜破损.5,10和100 nmol·L^(-1)的Antimycin⁃1处理MDA⁃MB⁃231细胞12,24和48 h引发细胞凋亡和坏死数量增加,并呈现时间和剂量依赖性.5,10和20 nmol·L^(-1)的Antimycin⁃1处理MDA⁃MB⁃231细胞6,12和24 h后,没有观察到对细胞周期时相的明显影响.20 nmol·L^(-1)的Antimycin⁃1处理MDA⁃MB⁃231细胞12,16,20和24 h后,引起胞内活性氧(reactive oxygen species,ROS)水平随处理时间延长呈逐渐下降趋势.以上结果证明,纳摩尔级的Antimycin⁃1能有效抑制和杀伤三阴性乳腺癌MDA⁃MB⁃231细胞.
In current work,the inhibitory and killing effects of Antimycin on Triple Negative Breast Cancer cell MDA⁃MB⁃231 were studied.Three natural products with similar structure,Antimycin⁃1,⁃2 and⁃3,had strong inhibitory effects on the growth of MDA⁃MB⁃231 cells.And the IC50 were 1.34±0.07,160±20 and 180±50 nmol·L^(-1),respectively.The activity of Antimycin⁃1 was about one hundred times higher than that of Antimycin⁃2 and Antimycin⁃3.10 nmol·L^(-1) Antimycin⁃1 could effectively inhibit the proliferation of MDA⁃MB⁃231 cells and the inhibition rates were about 80%and 90%after 24 h and 48 h treatment.The morphology of MDA⁃MB⁃231 cells were observed after treated with different concentrations of Antimycin1.10 and 100 nmol·L^(-1) of Antimycin⁃1 killed most MDA⁃MB⁃231 cells.1000 nmol·L^(-1) concentration of Antimycin⁃1 made the cells almost dissolve,leaving the nucleus and cytoplasmic debris.However,the morphology of MCF⁃10A cells and HCT116 cells were not significantly changed at the same concentrations of drugs.20 and 50 nmol·L^(-1) Antimycin⁃1 also significantly changed the nuclear morphology of MDA⁃MB⁃231 cells.The nucleus showed deformity,severe shrinkage and nuclear membrane damage.Treated with antimycin⁃1 at 5,10,100 nmol·L^(-1) concentrations for 12,24 and 48 h,the numbers of apoptosis and necrosis of MDA⁃MB⁃231 cells increased in a time and dose⁃dependent manner.After treatment with Antimycin⁃1 at concentrations of 5,10 and 20 nmol·L^(-1) for 6,12 and 24 h,no significant effects on cell cycle phase of MDA⁃MB⁃231 were observed.And the level of ROS(reactive oxygen species)in MDA⁃MB⁃231 cells decreased gradually with the prolongation of treatment time,after MDA⁃MB⁃231 cells were treated with 20 nmol·L^(-1) Antimycin⁃1.These results showed that Antimycin⁃1 at nanomolar concentration could effectively inhibit and kill MDA⁃MB⁃231 cells.
作者
郭怡
姜成燕
焦瑞华
蒋爱芹
Guo Yi;Jiang Chengyan;Jiao Ruihua;Jiang Aiqin(Center of Translational Medicine,Jiangsu Key Laboratory of Molecular Medicine,Nanjing University Medical School,Nanjing University,Nanjing,210008,China;State Key Laboratory of Pharmaceutical Biotechnology,Institute of Functional Bimolecular,School of Life Sciences,Nanjing University,Nanjing,210023,China)
出处
《南京大学学报（自然科学版）》
CAS
CSCD
北大核心
2021年第2期334-343,共10页
Journal of Nanjing University（Natural Science）
基金
国家自然科学基金(81301943)
南京大学双创示范基地重点项目(2017)。
