poly(I:C) synergizes with proteasome inhibitors to induce apoptosis in cervical cancer cells
| Autor: | Xueqiong Meng, Xiaoxi Cui, Xiaoya Shao, Yanqi Liu, Yihao Xing, Victoria Smith, Shiqiu Xiong, Salvador Macip, Yixiang Chen |
|---|---|
| Přispěvatelé: | Henan University of Science and Technology, University of Leicester, Universitat Oberta de Catalunya |
| Rok vydání: | 2022 |
| Předmět: |
combination
Cancer Research inhibidor del proteasoma combinació cervical cancer proteasome inhibitor apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens Apoptosis combinación poly(I.C.) cancer cervical oncologia Oncology Combination oncology Cervical cancer Proteasome inhibitor poly(I:C) oncología RC254-282 |
| Zdroj: | O2, repositorio institucional de la UOC Universitat Oberta de Catalunya (UOC) Translational Oncology, Vol 18, Iss, Pp 101362-(2022) |
| DOI: | 10.1016/j.tranon.2022.101362 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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