Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK

Molecular Medicine Reports
Jun Beom ParkJi Young Sul

Abstract

5‑Fluorouracil (5‑FU) is one of the most commonly used chemotherapeutic agents for gastric cancer. Resistance to 5‑FU‑based chemotherapy remains the major obstacle in the treatment of gastric cancer. A growing body of evidence has suggested that adenosine monophosphate‑activated protein kinase (AMPK) is pivotal for chemoresistance. However, the mechanism by which AMPK regulates the chemosensitivity of gastric cancer remains unclear. In the present study, how corosolic acid enhanced the chemosensitivity of gastric cancer cells to 5‑FU via AMPK activation was investigated. A 5‑FU‑resistant gastric cancer cell line (SNU‑620/5‑FUR) was established, which had a marked increase in thymidine synthase (TS) expression but reduced AMPK phosphorylation when compared with the parental cell line, SNU‑620. AMPK regulation by 5‑aminoimidazole‑4‑carboxamide ribonucleotide or compound c was revealed to be markedly associated with TS expression and 5‑FU‑resistant cell viability. In addition, corosolic acid activated AMPK, and decreased TS expression and the phosphorylation of mammalian target of rapamycin/4E‑binding protein 1 in a dose‑dependent manner. Corosolic acid treatment significantly reduced cell viability while compound c reversed coros...Continue Reading

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Citations

Jun 3, 2021·International Journal of Molecular Sciences·Jung Ho HanKi-Tae Ha
Jul 6, 2021·Frontiers in Oncology·Yue DengHuiming Peng

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Methods Mentioned

BETA
Protein Assay
electrophoresis

Software Mentioned

SPSS

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