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溶瘤呼肠孤病毒以TLR3依赖的方式诱导卵巢癌细胞凋亡。

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

作者信息

An Yuanyuan, Wang Xianyao, Wu Xuxian, Chen Liang, Yang Yichen, Lin Xiaojin, Wang Nianxue, Duan Jiangyao, Long Shiqi, Zhao Xing

机构信息

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.

Center for Stem Cell and Tissue Engineering Research, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, China.

出版信息

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.

摘要

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,其五年生存率低于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对呼肠孤病毒仍表现出抗性。为了解决卵巢癌治疗中的这种抗性问题,我们选择了对呼肠孤病毒耐药的OV-90卵巢癌细胞来研究呼肠孤病毒的溶瘤作用。我们发现,在转染呼肠孤病毒双链RNA(dsRNA)基因组后,OV-90细胞的活力下降。有趣的是,我们观察到OV-90细胞中Toll样受体3(TLR3)-dsRNA结合复合物的化学阻断以及下游TLR3信号传导的抑制破坏了呼肠孤病毒dsRNA触发的OV-90细胞凋亡。这些结果共同表明,呼肠孤病毒dsRNA通过TLR3信号通路诱导对呼肠孤病毒耐药的肿瘤细胞凋亡。

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