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

原儿茶酸与5-氟尿嘧啶联合作用对胃腺癌细胞p53基因表达及凋亡的影响

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

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 p53 gene expression and downregulation of Bcl-2 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 p53 and Bcl-2 signaling pathways.

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, p53 gene expression, and Bcl-2 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 p53 and downregulation of Bcl-2 protein when compared to the untreated control cells.

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