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

Xing-Xing He1, Chen-Kai Huang1, Bu-Shan Xie1

  • 1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Molecular Medicine Reports
|March 8, 2018
PubMed

Insights

5-fluorouracil (5-FU) induces apoptosis in gastric cancer cells. Inhibiting autophagy in BGC-823 cells enhances 5-FU

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The precise molecular mechanisms of 5-fluorouracil (5-FU) in human gastric cancer remain unclear.
  • Understanding 5-FU's effects on autophagy is crucial for improving gastric cancer treatment.

Purpose of the Study:

  • To elucidate the role of autophagy in 5-FU-induced cell death in human gastric cancer cell lines.
  • To investigate the involvement of sirtuin proteins in 5-FU-mediated autophagy and cell death.

Main Methods:

  • Treatment of BGC-823 and AGS gastric cancer cells with 5-FU.
  • Assessment of autophagosome formation via LC3 puncta, LC3 conversion, and electron microscopy.
  • Inhibition of autophagy using 3-methyladenine (3-MA) and beclin-1 ablation.
  • Analysis of sirtuin (SIRT1, SIRT3, SIRT5, SIRT6) expression using RT-qPCR and pharmacological inhibition with sirtinol.

Main Results:

  • 5-FU treatment induced apoptosis and inhibited proliferation in both cell lines.
  • Autophagy was promoted by 5-FU exclusively in BGC-823 cells.
  • Inhibition of autophagy significantly increased 5-FU-induced cell death in BGC-823 cells.
  • 5-FU treatment altered sirtuin expression, suggesting their involvement in regulating 5-FU-induced autophagy.

Conclusions:

  • Autophagy plays a complex role in 5-FU's efficacy against gastric cancer, specifically enhancing cell death in certain contexts.
  • Targeting sirtuin proteins offers a potential strategy to modulate autophagy and improve the therapeutic effectiveness of 5-FU in gastric carcinoma.
Keywords:
autophagyapoptosis5-FUsirtuins

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