Journal
TRANSLATIONAL ONCOLOGY
Volume 18, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101362
Keywords
Cervical cancer; poly(I:C); Proteasome inhibitor; Combination; Apoptosis
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Funding
- Henan University of Science and Technology [13480052, 13480048]
- M.C. Andreu Memorial Fund
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The combination of dsRNA poly(I:C) and proteasome inhibitors synergistically induce apoptosis in cervical cancer cells by activating multiple pro-apoptotic pathways, suggesting a potential therapeutic combination.
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 IFN beta 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-kappa B 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.
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