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The Sigma-2 Receptor/TMEM97 Agonist PB28 Suppresses Cell Proliferation and Invasion by Regulating the PI3K-AKT-mTOR

Bo Zhan1, Zhe Zhang1, Chiyuan Piao1

  • 1Department of Urology, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Journal of Cellular and Molecular Medicine
|November 16, 2021
PubMed

Insights

PB28, a sigma-2 receptor ligand, effectively inhibits renal cancer cell proliferation, migration, and invasion. This compound targets the PI3K-AKT-mTOR pathway and enhances cisplatin efficacy, showing promise as a cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Sigma-2 receptor (TMEM97) is overexpressed in various tumors.
  • Sigma-2 receptor ligands are being explored for cancer treatment strategies.

Purpose of the Study:

  • To evaluate the anti-cancer effects of PB28 on renal cancer cells.
  • To investigate PB28's impact on proliferation, migration, and invasion in vitro and in vivo.
  • To explore PB28's mechanism of action via the PI3K-AKT-mTOR pathway and its potential as a cisplatin sensitizer.

Main Methods:

  • In vitro assays: cell proliferation, migration, and invasion assays using renal cancer cell lines (786-O, ACHN, OS-RC-2).
  • In vivo studies: therapeutic effect evaluation in nude mice bearing renal tumors.
  • Molecular analysis: Western blot to assess PI3K-AKT-mTOR pathway protein phosphorylation.
  • Combination therapy assessment using CCK-8 assay with PB28 and cisplatin.

Main Results:

  • PB28 significantly inhibited proliferation, migration, and invasion of 786-O and ACHN cells in vitro.
  • PB28 demonstrated significant inhibition of tumor growth and invasion in vivo.
  • PB28 treatment led to decreased phosphorylation of key proteins in the PI3K-AKT-mTOR pathway.
  • The combination of PB28 and cisplatin enhanced the inhibition of renal cancer cell proliferation.

Conclusions:

  • PB28 exhibits potent anti-tumor activity against renal cancer by suppressing proliferation, migration, and invasion.
  • PB28 exerts its effects through the regulation of the PI3K-AKT-mTOR signaling pathway.
  • PB28 shows potential as a sensitizer to enhance the efficacy of cisplatin in renal cancer treatment.
Keywords:
Drug ResistanceEMTPB28PI3K-AKT-mTOR pathwayRenal cancerSigma-2/TMEM97

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