Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK
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
References
Thymidylate synthase gene amplification in human colon cancer cell lines resistant to 5-fluorouracil
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis