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Autophagy inhibition enhanced 5FUinduced cell death in human gastric carcinoma BGC823 cells

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The exact molecular mechanism of 5-fluorouracil (5-FU) in human gastric cancer cells remains to be elucidated. Cultured BGC823 human gastric carcinoma and AGS cell lines were treated with 5FU. Autophagosome formation was investigated through multiple approaches, including the quantification of green fluorescent proteinmicrotubuleassociated protein 1A/1Blight chain 3 (LC3) puncta, LC3 conversion and electron microscopy observations. Additionally, autophagy was inhibited using 3methyladenine (3MA) and beclin1 ablation, to determine its role in 5FUmediated cell death. In addition, the present study assessed alterations in sirtuin expression following 5FU treatment with reverse transcriptionquantitative polymerase chain reaction. 5FU treatment induced apoptosis and inhibited proliferation in BGC823 and AGS gastric cancer cells. It is of note that the 5FU treatment only promoted autophagy in BGC823 cells. Additionally, inhibition of autophagy by either 3MA or beclin1 ablation increased 5FUinduced cell death in BGC823 cells. The present study quantified changes in sirtuin (SIRT1, SIRT3, SIRT5, and SIRT6) expression following 5FU treatment and using a specific inhibitor, sirtinol, the present study investigated their involvement in 5FUmediated autophagy. Autophagy inhibition through manipulation of sirtuin proteins may increase the therapeutic efficacy of the 5FU chemotherapeutic drug against gastric carcinoma.
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Document Type: Research Article

Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China

Publication date: January 1, 2018

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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