1. Academic Validation
  2. Oncolytic reovirus induces ovarian cancer cell apoptosis in a TLR3-dependent manner

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.
Yuanyuan An 1 Xianyao Wang 1 Xuxian Wu 2 Liang Chen 3 Yichen Yang 2 Xiaojin Lin 1 Nianxue Wang 2 Jiangyao Duan 4 Shiqi Long 2 Xing Zhao 5
Affiliations

Affiliations

  • 1 Center 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.
  • 2 Center for Stem Cell and Tissue Engineering Research, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China.
  • 3 Department of Thoracic Breast Surgery, Anshun People's Hospital, Anshun, 561000, China.
  • 4 Department of Life Sciences, Imperial College London, London, SW7 2AZ, United Kingdom.
  • 5 Center 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; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. Electronic address: xingzhao@gmc.edu.cn.
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.

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