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Title: poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells
Author: Meng, Xueqiong
Cui, Xiaoxi  
Shao, Xiaoya
Liu, Yanqi  
Xing, Yihao  
Smith, Victoria  
Xiong, Shiqiu  
Macip Maresma, Salvador  
Chen, Yixiang  
Others: Henan University of Science and Technology
University of Leicester
Universitat Oberta de Catalunya
Keywords: cervical cancer
proteasome inhibitor
Issue Date: 2-Apr-2022
Publisher: Translational Oncology
Published in: 18
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Abstract: Cervical cancer is one of the most common malignancies in women, with a poor survival rate. Thus, there is a need to define effective combination strategies to improve therapy. In this study, we report that dsRNA poly(I:C) up-regulated the expression of IFNβ and apoptosis-associated genes in cervical cancer cells, activating both intrinsic and extrinsic apoptotic pathways, and eventually inducing cell death. Similarly, proteasome inhibitors also effectively induced cervical cancer cell apoptosis, probably through prevention of p53 degradation, inhibiting NF-κB signal activation and decreasing BCL-2 expression. Importantly, the combination of poly(I:C) with proteasome inhibitors enhanced caspase-8 and caspase-9 activation, and synergistically induced cervical cancer cell apoptosis. Both activated p38 signals and increased ROS levels, and their combination extended these effects. Collectively, we show that the activation of multiple pro-apoptotic pathways by poly(I:C) and proteasome inhibitors underpin a synergistic effect on inducing cervical cancer cell death, suggesting a potential therapeutic combination with clinical relevance.
Language: English
ISSN: 1936-5233MIAR
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