Rigosertib potently protects against colitis-associated intestinal fibrosis and inflammation by regulating PI3K/AKT and NF-κB signaling pathways

Life Sciences
Farzad RahmaniSeyed Mahdi Hassanian

Abstract

Rigosertib (RGS) is a PI3K inhibitor that exerts protective effects against tumor progression and cancer-related inflammation. This study was aimed to explore the regulatory effects of RGS on proliferative, pro-fibrotic and inflammatory factors in DSS- induced colitis mice model. The present study integrates systems and molecular biology approaches to investigate the therapeutic potency of RGS in an experimental model of colitis specifically examining its effects on the PI3K/AKT and NF-κB signaling pathways. Analysis of time-resolved proteome profiling showed that PI3K-AKT inhibitors regulate expression of many proteins in all stages of inflammation, fibrogenesis and extracellular matrix remodeling. Consistent with our in-silico findings, RGS improved colitis disease activity as assessed by changes in body weight, degree of stool consistency, rectal bleeding and prolapse. RGS also reduced oxidative stress markers and colon histopathological score by decreasing inflammatory responses in colon tissues. Moreover, expression of pro-fibrotic and pro-inflammatory factors including Acta 2, Col 1a1, Col 1a2, IL-1β, TNF-α, INF-γ, and MCP-1 were suppressed in the mice treated with RGS compared to the control group. The protective effects...Continue Reading

Citations

Mar 27, 2021·Current Opinion in Gastroenterology·Muaad Abdulla, Thean Soon Chew
Apr 4, 2021·International Journal of Molecular Sciences·Sara LettieriGiulia Maria Stella
Jun 2, 2021·Immunity, Inflammation and Disease·Yin WangDonghui Jiang

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