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[Molecular Mechanisms of Apoptosis of Leukemia Cell Induced by Reovirus]

Chen Li1,2, Jing Mo1,2, Li-Ping Shu1,2

  • 1Tissue Engineering and Stem Cell Research Center, School of Basic Medical Sciences, Guizhou Medicine University, Guiyang 550004, China.

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition
|November 26, 2019
PubMed
Abstract

Insights

Oncolytic virus Reovirus type 3 (Reo3) effectively induces apoptosis in HL60 cancer cells by activating protein kinase R (PKR). Inhibiting PKR with 2-aminopurine (2-AP) significantly reduced Reo3-induced cell death, confirming PKR

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • Oncolytic viruses are promising cancer therapeutics.
  • Reovirus type 3 (Reo3) has shown oncolytic potential.
  • Understanding the molecular mechanisms of viral-induced apoptosis is crucial for optimizing cancer therapy.

Purpose of the Study:

  • To elucidate the molecular mechanism by which Reo3 induces apoptosis in HL60 cells.
  • To investigate the role of protein kinase R (PKR) in Reo3-mediated apoptosis.

Main Methods:

  • HL60 cells were infected with Reo3 at various multiplicities of infection (MOI).
  • Cell activity was assessed using CCK8 assay.
  • Apoptotic rates were determined by flow cytometry.
  • PKR activation and apoptotic protein expression were analyzed via Western blot.
  • The effect of the PKR inhibitor 2-aminopurine (2-AP) on apoptosis was evaluated.

Main Results:

  • Reo3 infection inhibited HL60 cell activity and increased apoptosis in a dose-dependent manner.
  • Reo3 upregulated the expression of PKR, phosphorylated PKR (p-PKR), Bax, Caspase-3, and cleaved Caspase-3, while downregulating Bcl-2.
  • Pretreatment with 2-AP significantly reduced Reo3-induced apoptosis, PKR phosphorylation, and apoptotic protein expression.

Conclusions:

  • Oncolytic virus Reo3 activates PKR in HL60 cells.
  • PKR activation is a key mediator of Reo3-induced apoptosis in HL60 cells.
  • Reo3 demonstrates potential as an oncolytic agent targeting leukemia cells via PKR-dependent apoptosis.
Keywords:
2-aminopurineApoptosisApoptosis-related proteinsHL60 cellsPKRReovirus

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