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

Virus Res. 2021 Aug:301:198440. doi: 10.1016/j.virusres.2021.198440. Epub 2021 Apr 30.

Abstract

Globally, ovarian cancer is the seventh most common cancer and the eighth-most common cause of cancer death among women with a five-year survival rate of less than 45%. Although reovirus is known to be effective for treating ovarian cancer, some types of tumor cells still exhibit resistance to reovirus. In order to solve this resistance problem in the treatment of ovarian cancer, we selected the reovirus-resistant OV-90 ovarian cancer cells to study reovirus oncolytic effects. We found that the viability of OV-90 cells decreased after reovirus double-stranded RNA (dsRNA) genome transfection. Interestingly, we observed that chemical blockage of the Toll-like receptor 3 (TLR3)-dsRNA binding complex in OV-90 cells and the inhibition of downstream TLR3 signaling disrupted OV-90 apoptosis triggered by reovirus dsRNA. Together, these results demonstrate that reovirus dsRNA induces reovirus-resistant tumor cell apoptosis through the TLR3 signaling pathway.

Keywords: Apoptosis; Double-stranded RNA; Ovarian cancer; Reovirus; Toll-like receptor 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Female
  • Humans
  • Oncolytic Virotherapy*
  • Ovarian Neoplasms* / therapy
  • RNA, Double-Stranded / genetics
  • Reoviridae* / genetics
  • Toll-Like Receptor 3* / genetics

Substances

  • RNA, Double-Stranded
  • TLR3 protein, human
  • Toll-Like Receptor 3