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Oncolytic reovirus induces ovarian cancer cell apoptosis in a TLR3-dependent manner

Yuanyuan An1, Xianyao Wang1, Xuxian Wu2

  • 1Center for Stem Cell and Tissue Engineering Research, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China; Key Laboratory of Adult Stem Cell Transformation Research, Guiyang, 550004, China.

Virus Research
|May 3, 2021
PubMed

Insights

Reovirus double-stranded RNA (dsRNA) can overcome resistance in ovarian cancer cells. This occurs through the Toll-like receptor 3 (TLR3) signaling pathway, triggering apoptosis in resistant tumor cells.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Ovarian cancer is a leading cause of cancer death in women, with a low five-year survival rate.
  • Reovirus shows promise for ovarian cancer treatment, but tumor cell resistance is a significant challenge.
  • Understanding mechanisms of reovirus resistance is crucial for improving therapeutic efficacy.

Purpose of the Study:

  • To investigate the oncolytic effects of reovirus in reovirus-resistant ovarian cancer cells (OV-90).
  • To elucidate the role of the Toll-like receptor 3 (TLR3) signaling pathway in reovirus-induced apoptosis of resistant ovarian cancer cells.

Main Methods:

  • Transfection of OV-90 cells with reovirus double-stranded RNA (dsRNA) genome.
  • Chemical blockage of the Toll-like receptor 3 (TLR3)-dsRNA binding complex.
  • Inhibition of downstream TLR3 signaling pathways.
  • Assessment of OV-90 cell viability and apoptosis.

Main Results:

  • Reovirus dsRNA transfection decreased the viability of OV-90 cells.
  • Blocking TLR3 or inhibiting its downstream signaling disrupted reovirus dsRNA-triggered apoptosis in OV-90 cells.
  • Reovirus dsRNA effectively induced apoptosis in resistant ovarian cancer cells.

Conclusions:

  • Reovirus dsRNA induces apoptosis in reovirus-resistant ovarian cancer cells.
  • The Toll-like receptor 3 (TLR3) signaling pathway is essential for reovirus dsRNA-mediated apoptosis in these resistant cells.
  • Targeting the TLR3 pathway may offer a strategy to overcome reovirus resistance in ovarian cancer treatment.
Keywords:
ApoptosisDouble-stranded RNAOvarian cancerReovirusToll-like receptor 3

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