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AMPK activator AICAR promotes 5-FU-induced apoptosis in gastric cancer cells.

Molecular and cellular biochemistry (2015-10-27)
Yan Wu, Yijun Qi, Hu Liu, Xiaoshan Wang, Huaqing Zhu, Zhengguang Wang
ABSTRACT

The aim of the present study was to determine the effect of AICAR, an AMPK activator, on apoptosis in gastric carcinoma cells (SGC-7901) with or without 5-fluorouracil (5-FU). SGC-7901 cells were treated with AICAR (0.2-5 mM, for 24-48 h) with or without 5-FU. Cell viability was determined using MTT assay, while apoptosis were measured through the evaluation of active caspase-3 activity and DNA fragmentation. Real-time PCR was employed to determine the expression of tumor suppressor and multi-drug resistant (mdr1) gene. Cleaved caspase-3 and phosphorylated AMPK (p-AMPK) were measured by Western blot. AICAR significant reduced cellular viability but increased apoptosis in a time- and dose-dependent manner, which is associated with an increase in p-AMPK levels. Importantly, AICAR enhanced the sensitivity to 5-FU-induced reduction of cellular viability and increased apoptosis in SGC-7901 cells. Furthermore, AICAR increased tumor suppressor genes [F-box and WD repeat domain containing 7 (FBXW7), semaphorin III/F (SEMA3F), and p21(Cip1) (p21)] but reduced mdr1 expression. Finally, p-AMPK levels were reduced in 5-FU-resistant gastric cancer cells compared to human immortalized gastric epithelial cell line and 5-FU-sensitive gastric cancer cells. AICAR not only induces apoptosis alone but also enhances pro-apoptotic effect of 5-FU in SGC-7901 cells, which lays an experimental foundation to develop AICAR as a chemotherapeutic sensitizer against gastric cancer.

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Sigma-Aldrich
AICAR, ≥98% (HPLC), powder