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Ketamine Inhibits Ovarian Cancer Cell Growth by Regulating the lncRNA-PVT1/EZH2/p57 Axis

Tao Li1, Jie Yang2, Ben Yang3

  • 1Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Changchun, China.

Frontiers in Genetics
|March 25, 2021
PubMed

Insights

Ketamine inhibits ovarian cancer cell growth by affecting cell cycle and apoptosis. This study reveals ketamine

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ketamine is used for cancer pain and shows tumor cell growth inhibition.
  • The specific effects of ketamine on ovarian cancer and its molecular mechanisms remain unclear.

Purpose of the Study:

  • To investigate the effect of ketamine on ovarian cancer cell proliferation, survival, and cell cycle.
  • To explore the molecular mechanisms underlying ketamine's action in ovarian cancer, focusing on long non-coding RNAs (lncRNAs).

Main Methods:

  • Testing ketamine's effect on six ovarian cancer cell lines.
  • Bioinformatic analysis of a GEO dataset to identify altered lncRNAs.
  • Investigating ketamine's regulation of lncRNA PVT1, P300-mediated acetylation, and EZH2 binding.
  • RNA immunoprecipitation to confirm PVT1-EZH2 interaction and downstream gene regulation.

Main Results:

  • Ketamine significantly inhibited ovarian cancer cell proliferation and survival.
  • Ketamine induced cell cycle arrest, apoptosis, and reduced colony formation.
  • Ketamine altered the expression of specific lncRNAs, notably PVT1, through P300-mediated epigenetic modification.
  • PVT1 was found to bind EZH2, influencing the expression of target genes like p57 and affecting ovarian cancer cell biology.

Conclusions:

  • Ketamine exhibits significant anti-ovarian cancer activity by impacting cell cycle, apoptosis, and lncRNA expression.
  • The study elucidates a novel mechanism involving lncRNA PVT1, EZH2, and epigenetic modifications in ketamine's anti-cancer effects.
  • Ketamine presents a potential therapeutic strategy for ovarian cancer.
Keywords:
histone acetylationketaminelncRNAovarian cancerp300

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