Rapamycin suppresses the PI3K/AKT/mTOR signaling pathway by targeting SIRT1 in esophageal cancer

Tao Liu1,2, Xiangsen Liang2, Yu Sun2

  • 1Department of Cardiothoracic Surgery, Guangxi International Zhuang Medical Hospital, Nanning, Guangxi 530201, P.R. China.

Insights

Rapamycin

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Rapamycin exhibits antitumor and immunosuppressive properties.
  • The role of rapamycin in human esophageal cancer (EC) treatment is not well understood.
  • Sirtuin 1 (SIRT1) is implicated in various cellular processes and cancer.

Purpose of the Study:

  • To investigate the antitumoral effects of rapamycin in human esophageal cancer (EC).
  • To explore the role of sirtuin 1 (SIRT1) in mediating rapamycin's effects on EC.
  • To analyze the impact of rapamycin and SIRT1 modulation on the PI3K/AKT/mTOR pathway in EC.

Main Methods:

  • Quantification of SIRT1 mRNA expression using reverse transcription-quantitative PCR.
  • Measurement of SIRT1 and PI3K/AKT/mTOR protein levels via western blotting.
  • Assessment of cell viability, migration, and invasion using CCK-8, wound healing, and Transwell assays.
  • In vivo studies using mouse models with manipulated SIRT1 expression.

Main Results:

  • SIRT1 expression was found to be upregulated in EC tissues and cell lines.
  • Rapamycin's inhibitory effects on EC cell viability, migration, and invasion were modulated by altering SIRT1 levels.
  • SIRT1 overexpression rescued rapamycin's inhibitory effects, while SIRT1 knockdown enhanced them.
  • Rapamycin treatment led to decreased phosphorylation of PI3K, AKT, and mTOR, which was reversed by SIRT1 transfection.

Conclusions:

  • Rapamycin demonstrates potential in suppressing esophageal cancer progression.
  • The study identifies SIRT1 as a key regulator in rapamycin's antitumoral mechanism in EC.
  • Rapamycin exerts its effects by negatively regulating SIRT1 and inhibiting the PI3K/AKT/mTOR signaling pathway.

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