1. Academic Validation
  2. poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells

poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells

  • Transl Oncol. 2022 Apr;18:101362. doi: 10.1016/j.tranon.2022.101362.
Xueqiong Meng 1 Xiaoxi Cui 1 Xiaoya Shao 1 Yanqi Liu 1 Yihao Xing 1 Victoria Smith 2 Shiqiu Xiong 2 Salvador Macip 3 Yixiang Chen 4
Affiliations

Affiliations

  • 1 School of Basic Medical Science, Henan University of Science and Technology, Luoyang, China.
  • 2 Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, United Kingdom.
  • 3 Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, United Kingdom; Mechanisms of Cancer and Ageing Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom; FoodLab, Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain.
  • 4 School of Basic Medical Science, Henan University of Science and Technology, Luoyang, China. Electronic address: ychen174@163.com.
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.

Keywords

Apoptosis; Cervical cancer; Combination; Proteasome inhibitor; poly(I:C).

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