Oncolytic reovirus induces ovarian cancer cell apoptosis in a TLR3-dependent manner
Oncolytic reovirus induces ovarian cancer cell apoptosis in a TLR3-dependent manner
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溶瘤呼肠孤病毒以 TLR3 依赖性方式诱导卵巢癌细胞凋亡
DOI：
10.1016/j.virusres.2021.198440
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发表时间：
2021-05-25
期刊：
影响因子：
5
通讯作者：
Zhao, Xing
中科院分区：
文献类型：
--
作者：
An, Yuanyuan;Wang, Xianyao;Zhao, Xing
在全球范围内，卵巢癌是第七大常见癌症，也是女性癌症死亡的第八大常见原因，五年生存率低于45%。尽管已知呼肠孤病毒对治疗卵巢癌有效，但某些类型的肿瘤细胞仍表现出对呼肠孤病毒的抗性。为了解决卵巢癌治疗中的这种耐药问题，我们选择呼肠孤病毒耐药的OV-90卵巢癌细胞来研究呼肠孤病毒的溶瘤作用。我们发现，OV-90细胞的活力下降后，呼肠孤病毒双链RNA（dsRNA）基因组转染。有趣的是，我们观察到OV-90细胞中Toll样受体3（TLR 3）-dsRNA结合复合物的化学阻断和下游TLR 3信号传导的抑制破坏了由呼肠孤病毒dsRNA触发的OV-90细胞凋亡。总之，这些结果表明呼肠孤病毒dsRNA通过TLR 3信号传导途径诱导呼肠孤病毒抗性肿瘤细胞凋亡。
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.