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The Pro-tumor and Anti-tumor Effects of NLRP3 Inflammasome as a New Therapeutic Option for Colon Cancer: a Meta-analysis of Pre-clinical Studies

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Abstract

In this review, we aimed to elaborate on these findings and explore how NLRP3 inflammasome affects CRC and which mechanism could be a potential therapeutic target. For this purpose, major indexing databases consist of Cochrane central, ISI web of science (WOS), PubMed/Medline, Scopus, and EMBASE were systematically searched using standard terms without any language, study region, or type restrictions. After applying the exclusion criteria, the main properties of 12 articles on 326 animals included in this meta-analysis. Of 12, eight were about an anti-tumoral effect, and four were on a pro-tumoral effect of the inflammasome. NLRP3 inhibition reduced IL-1β (SMD: −4.14, 95% CI: −5.49, −2.79, P < 0.00001, I2 = 76%), TNFα (SMD: −2.18, 95% CI: −3.23, −1.13, P < 0.00001, I2 = 82%), and IL-18 (SMD: −2.27, 95% CI: −3.38, −1.16, P = 0.0002, I2 = 74%) significantly contrasted with the model controls. Colons harvested from NLRP3 inhibition groups showed significant truncation compared with the model controls (SMD: −1.75, 95% CI: −2.69, −0.81, P = 0.0003, I2 = 60%). We demonstrated significantly decreased tumorigenesis following NLRP3 inactivation, as well as an increased survival rate compared with the model controls. To translate anti-cancer agents based on anti-NLRP3 from bench to bedside, it is necessary to identify the molecules that selectively target NLRP3 or its downstream pathways in malignant cells, as well as considering metabolic heterogeneity and the mechanisms causing such cancer-connected heterogeneity. Other studies are needed to separate the molecular and functional complexity of this network.

Summary

Secretion of IL-1β is contingent upon activation of the inflammasome complex of NLRP3. It has been suggested that activation of this complex necessitates two signals. One of these signals is made available by activation of toll-like-receptor (TLR)-mediated NF-kappa and actuates the IL-1β precursor synthesis and NLRP3 assembly. Another signal is conceivable to be mediated by hazard signals e.g., the purinergic P2X7 receptor stimulated by Adenosine triphosphate or other stimuli resulting in the efflux of potassium.

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Authors and Affiliations

  1. Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Majid Ghanawat

  2. Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Babak Arjmand

  3. Thalassemia and Hemoglobinopathy Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Fakher Rahim

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Ghanawat, M., Arjmand, B. & Rahim, F. The Pro-tumor and Anti-tumor Effects of NLRP3 Inflammasome as a New Therapeutic Option for Colon Cancer: a Meta-analysis of Pre-clinical Studies. J Gastrointest Canc 54, 227–236 (2023). https://doi.org/10.1007/s12029-022-00805-3

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