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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

Felix J Kim1, Joel M Schrock, Christina M Spino

  • 1Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102-1192, USA. fkim@drexelmed.edu

Biochemical and Biophysical Research Communications
|August 29, 2012
PubMed

Insights

Sigma1 receptor ligands inhibit cancer cell growth by repressing protein synthesis. Targeting sigma1 receptor (Sigma1) with antagonists decreases cell mass and translation, offering potential cancer therapy strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sigma1 receptor (Sigma1) ligands inhibit cancer cell proliferation and tumor growth.
  • The precise cellular mechanisms underlying Sigma1 ligand effects on cancer cells are not fully understood.

Purpose of the Study:

  • To investigate the role of Sigma1 in regulating cancer cell protein synthesis.
  • To determine if Sigma1 antagonists can modulate protein translation in cancer cells.

Main Methods:

  • Treatment of breast and prostate cancer cell lines with Sigma1 antagonists.
  • Assessment of cell mass and cap-dependent translation initiation.
  • Analysis of phosphorylation of key translational regulator proteins (p70S6K, S6, 4E-BP1).
  • RNA interference (RNAi)-mediated knockdown of Sigma1.

Main Results:

  • Sigma1 antagonist treatment decreased cancer cell mass and repressed cap-dependent translation initiation.
  • Suppression of phosphorylation of p70S6K, S6, and 4E-BP1 was observed.
  • Sigma1 knockdown mimicked the effects of antagonist treatment, causing translational repression.
  • The observed effects on translational repression and cell size were reversible.

Conclusions:

  • Sigma1 plays a significant role in regulating protein synthesis in tumor cells.
  • Small molecule Sigma1 ligands can effectively modulate protein translation.
  • Sigma1 antagonists represent a potential therapeutic strategy for targeting cancer cell protein synthesis.

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