广西医科大学学报2019，Vol.36Issue(2)：163-168,6.DOI:10.16190/j.cnki.45-1211/r.2019.02.001
新型大黄酸衍生物4F抑制MCF-7细胞增殖并通过旁凋亡途径诱导细胞死亡
A novel Rhein derivative 4F anti-proliferation via paraptosis-like cell death in MCF-7 cells
摘要
Abstract
Objective:To investigate the effects and molecular mechanisms of Rhein and the Rhein derivative 4F on proliferation,submicrostructure and induced cell death on MCF-7 cell line in vitro.Methods:CCk-8 assay,colony formation assay and cell apoptosis were used to compare the anti-tumor effects among 4F,Rhein and Cisplatin on the breast cancer cell line MCF-7.The vacuoles in MCF-7 cells were observed by transmission electron microscopy (TEM).Western blotting was used to determine paraptosis,autophagy and apoptosis-related proteins including p62,microtubule-associated proteins light chain 3 (LC3),glucose-regulated protein (Grp) 78,cleaved caspase-9 and caspase-7.Results:4F had better cytotoxicity than Rhein (P＜0.05),and it had no influence on cells apoptosis ratio.Accumulation of cytoplasmic vacuoles and swollen mitochondrias were observed in 4F-treated MCF-7 cells,accompanied by the higher expression of Grp78 (P ＜ 0.05).However,apoptosis related protein cleaved caspase-9 and caspase-7 levels remained unchanged in 4F treated cells (P ＞ 0.05).Conclusion:4 F induced cell death in MCF7 cells linked to paraptosis,a non-apoptosis and non autophagy cell death.4F maybe an alternative drug candidate immune to apoptotic drug resistance.关键词
细胞质空泡/旁凋亡/细胞死亡/乳腺癌MCF-7细胞系/大黄酸Key words
cytoplasmic vacuoles/paraptosis/cell death/breast cancer MCF-7 cell lines/Rhein分类
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刘云风,田炜,蓝富,亢健康,庞会锋,侯华新,黎丹戎..新型大黄酸衍生物4F抑制MCF-7细胞增殖并通过旁凋亡途径诱导细胞死亡[J].广西医科大学学报,2019,36(2):163-168,6.基金项目
The present study was supported by the National Natural Science Foundation of China (No.81460561 and No.81360502),Guangxi Natural Science Foundation (No.2014GXNSFAA118225) and the Program of Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University),the Ministry of Education,China (No.GKE2018-09 and No.GK2018-11). （No.81460561 and No.81360502）
