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

Translational Oncology

Yixiang Chen¹  Shiqiu Xiong²  Salvador Macip²  Victoria Smith²  Yanqi Liu³  Xueqiong Meng³  Xiaoxi Cui³  Xiaoya Shao³  Yihao Xing³ 

[1] Mechanisms of Cancer and Ageing Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom;Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, United Kingdom;School of Basic Medical Science, Henan University of Science and Technology, Luoyang, China;

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

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown