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

  • Authors:
    • Xing‑Xing He
    • Chen‑Kai Huang
    • Bu‑Shan Xie
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  • Published online on: March 1, 2018     https://doi.org/10.3892/mmr.2018.8661
  • Pages: 6768-6776
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Abstract

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.
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May-2018
Volume 17 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
He XX, Huang CK and Xie BS: Autophagy inhibition enhanced 5‑FU‑induced cell death in human gastric carcinoma BGC‑823 cells. Mol Med Rep 17: 6768-6776, 2018
APA
He, X., Huang, C., & Xie, B. (2018). Autophagy inhibition enhanced 5‑FU‑induced cell death in human gastric carcinoma BGC‑823 cells. Molecular Medicine Reports, 17, 6768-6776. https://doi.org/10.3892/mmr.2018.8661
MLA
He, X., Huang, C., Xie, B."Autophagy inhibition enhanced 5‑FU‑induced cell death in human gastric carcinoma BGC‑823 cells". Molecular Medicine Reports 17.5 (2018): 6768-6776.
Chicago
He, X., Huang, C., Xie, B."Autophagy inhibition enhanced 5‑FU‑induced cell death in human gastric carcinoma BGC‑823 cells". Molecular Medicine Reports 17, no. 5 (2018): 6768-6776. https://doi.org/10.3892/mmr.2018.8661