Autophagy inhibition enhanced 5‑FU‑induced cell death in human gastric carcinoma BGC‑823 cells.

The exact molecular mechanism of 5-fluorouracil (5-FU) in human gastric cancer cells remains to be elucidated. Cultured BGC‑823 human gastric carcinoma and AGS cell lines were treated with 5‑FU. Autophagosome formation was investigated through multiple approaches, including the quantification of green fluorescent protein‑microtubule‑associated protein 1A/1B‑light chain 3 (LC3) puncta, LC3 conversion and electron microscopy observations. Additionally, autophagy was inhibited using 3‑methyladenine (3‑MA) and beclin‑1 ablation, to determine its role in 5‑FU‑mediated cell death. In addition, the present study assessed alterations in sirtuin expression following 5‑FU treatment with reverse transcription‑quantitative polymerase chain reaction. 5‑FU treatment induced apoptosis and inhibited proliferation in BGC‑823 and AGS gastric cancer cells. It is of note that the 5‑FU treatment only promoted autophagy in BGC‑823 cells. Additionally, inhibition of autophagy by either 3‑MA or beclin‑1 ablation increased 5‑FU‑induced cell death in BGC‑823 cells. The present study quantified changes in sirtuin (SIRT1, SIRT3, SIRT5, and SIRT6) expression following 5‑FU treatment and using a specific inhibitor, sirtinol, the present study investigated their involvement in 5‑FU‑mediated autophagy. Autophagy inhibition through manipulation of sirtuin proteins may increase the therapeutic efficacy of the 5‑FU chemotherapeutic drug against gastric carcinoma.