Poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells
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Authors
Meng, Xueqiong
Cui, Xiaoxi
Shao, Xiaoya
Liu, Yanqi
Xing, Yihao
Smith, Victoria
Xiong, Shiqiu
Macip, Salvador
Chen, Yixiang
Issue Date
2022-02-09
Type
Article
Language
en_US
Keywords
Cervical Cancer , poly(I:C) , Proteasome Inhibitor , Combination , Apoptosis
Alternative Title
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.
Description
Citation
Meng, X., Cui, X., Shao, X., Liu, Y., Xing, Y., Smith, V., Xiong, S., Macip, S., & Chen, Y. (2022). poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells. Translational oncology, 18, 101362. https://doi.org/10.1016/j.tranon.2022.101362
Publisher
Translational Oncology