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p53基因表达的激活以及5-氟尿嘧啶和β-七叶皂苷对MCF7细胞的协同抗增殖作用

Activation of p53 Gene Expression and Synergistic Antiproliferative Effects of 5-Fluorouracil and β-escin on MCF7 Cells.

作者信息

Mazrouei Raziyeh, Raeisi Elham, Lemoigne Yves, Heidarian Esfandiar

机构信息

Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Medical Physics and Radiology, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

J Med Signals Sens. 2019 Aug 29;9(3):196-203. doi: 10.4103/jmss.JMSS_44_18. eCollection 2019 Jul-Sep.

Abstract

One of the most common malignancies in women is breast cancer. β-escin has pharmacological anticancer effects. 5-fluorouracil (5-FU) has antimetabolite and antiproliferative properties. The purpose of this study was to investigate the combined effects of 5-FU and β-escin on apoptosis, colony formation, Bcl-2 signaling protein, and p53 gene expression in MCF7 breast cancer cell line. The cytotoxic effects, the number of colonies, apoptosis, p53 gene expression, and Bcl-2 signaling protein of the combined 5-FU and β-escin on MCF7 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and western blotting methods, respectively. Half-maximal inhibitory concentration values of β-escin and 5-FU were 80 μg/ml and 2 μM, respectively. The combination of 5-FU and β-escin on MCF7 cell viability showed a combination index equal to 0.5. The expression of p53 and apoptosis increased in the combination of 5-FU and β-escin on MCF7 cells compared to that of control group ( < 0.05). In addition, the number of colonies and Bcl-2 signaling protein in combination of 5-FU and β-escin decreased with respect to untreated control cells or single treatment of 5-FU and β-escin. The combination of 5-FU and β-escin not only has synergistic effects by increasing cell apoptosis and p53 gene expression but also decreases Bcl-2 signaling protein in MCF7 cell lines.

摘要

乳腺癌是女性最常见的恶性肿瘤之一。β-七叶皂苷具有药理抗癌作用。5-氟尿嘧啶(5-FU)具有抗代谢和抗增殖特性。本研究的目的是探讨5-FU与β-七叶皂苷联合应用对MCF7乳腺癌细胞系凋亡、集落形成、Bcl-2信号蛋白和p53基因表达的影响。分别采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、克隆形成试验、流式细胞术、实时定量聚合酶链反应和蛋白质印迹法测定5-FU与β-七叶皂苷联合应用对MCF7细胞的细胞毒性作用、集落数量、凋亡、p53基因表达和Bcl-2信号蛋白。β-七叶皂苷和5-FU的半数最大抑制浓度值分别为80μg/ml和2μM。5-FU与β-七叶皂苷联合应用对MCF7细胞活力的联合指数等于0.5。与对照组相比,5-FU与β-七叶皂苷联合应用于MCF7细胞时,p53表达和凋亡增加(<0.05)。此外,与未处理的对照细胞或5-FU和β-七叶皂苷单药处理相比,5-FU与β-七叶皂苷联合应用时的集落数量和Bcl-2信号蛋白减少。5-FU与β-七叶皂苷联合应用不仅通过增加细胞凋亡和p53基因表达产生协同作用,而且还降低了MCF7细胞系中的Bcl-2信号蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/6743244/1384a312535d/JMSS-9-196-g001.jpg

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