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原儿茶酸与5-氟尿嘧啶对胃腺癌细胞p53基因表达及细胞凋亡的联合作用

Combined Effects of Protocatechuic Acid and 5-Fluorouracil on p53 Gene Expression and Apoptosis in Gastric Adenocarcinoma Cells.

作者信息

Motamedi Zahra, Amini Sayed Asadollah, Raeisi Elham, Lemoigne Yves, Heidarian Esfandiar

机构信息

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

Shahrekord University of Medical Sciences, Basic Health Sciences Institute, Cellular and Molecular Research Center, Shahrekord, Iran.

出版信息

Turk J Pharm Sci. 2020 Dec 23;17(6):578-585. doi: 10.4274/tjps.galenos.2019.69335.

Abstract

OBJECTIVES

This study evaluated the combined effects of protocatechuic acid (PCA) and 5-fluorouracil (5-FU) on gastric adenocarcinoma (AGS) cells.

MATERIALS AND METHODS

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry technique, real-time quantitative polymerase chain reaction, and Western blotting were used to investigate cytotoxic effects, colony formation, apoptosis, gene expression, and protein level in AGS cells treated with 5-FU and PCA.

RESULTS

Our results demonstrated that PCA (500 μM) alone or in combination with 5-FU (10 μM) inhibited AGS cell proliferation, inhibited a colony formation, and increased apoptosis compared with untreated control cells. Moreover, the combined 5-FU/PCA exposure led to upregulation of and downregulation of protein when compared to the untreated control cells.

CONCLUSION

The results demonstrate that the combined 5-FU/PCA may promote antiproliferative and pro-apoptotic effects with the inhibition of colony formation in AGS cells. The mechanisms by which the combined 5-FU/PCA exposure exerts its effects are associated with upregulation of gene expression and downregulation of level. Therefore, the combination of 5-FU with PCA not only could be a promising approach to potentially reduce the dose requirements of 5-FU but also could promote apoptosis via and signaling pathways.

摘要

目的

本研究评估了原儿茶酸(PCA)和5-氟尿嘧啶(5-FU)对胃腺癌(AGS)细胞的联合作用。

材料与方法

采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法、集落形成试验、流式细胞术、实时定量聚合酶链反应和蛋白质印迹法,研究5-FU和PCA处理的AGS细胞的细胞毒性作用、集落形成、凋亡、基因表达和蛋白质水平。

结果

我们的结果表明,与未处理的对照细胞相比,单独使用PCA(500μM)或与5-FU(10μM)联合使用均可抑制AGS细胞增殖、抑制集落形成并增加凋亡。此外,与未处理的对照细胞相比,5-FU/PCA联合处理导致 蛋白上调和 蛋白下调。

结论

结果表明,5-FU/PCA联合使用可能通过抑制AGS细胞集落形成来促进抗增殖和促凋亡作用。5-FU/PCA联合处理发挥其作用的机制与 基因表达上调和 水平下调有关。因此,5-FU与PCA联合使用不仅可能是一种有望降低5-FU剂量需求的方法,而且还可能通过 和 信号通路促进细胞凋亡。

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