Exploring the mechanism of Jianpi Lishi Jiedu Granules against postoperative recurrence of colorectal adenoma based on IL-6/JAK/STAT3 signaling pathway

Abstract

Globally, colorectal cancer (CRC) is the primary cause of cancer-related fatalities. Our previous study demonstrated the efficacy of Jianpi Lishi Jiedu Granules (JLJG) in preventing postoperative recurrence of colorectal adenoma (CRA). Building on this foundation, the current study aims to elucidate whether the mechanism by which JLJG prevents postoperative recurrence of CRA involves the classical JAK/STAT inflammatory signaling pathway and to assess its specific impact on this pathway. Utilizing proteomics, we discerned 143 differentially expressed proteins (DEPs) regulated by JLJG, whose functional roles are intimately linked to the JAK/STAT signaling pathway. Among these, we identified key proteins such as IL-6, JAK1, JAK2, STAT3, CCND1, MYC, Bcl-XL, and SOCS3 that are regulated by JLJG and play pivotal roles in the JAK/STAT signaling cascade. Our findings indicate that the sustained activation of the IL-6/JAK/STAT3 signaling pathway is significantly associated with CRA recurrence. JLJG was found to effectively modulate the expression levels of these proteins, as well as the expression of downstream genes including BCL2, MCL1, P21, and JAK1, STAT3, thereby inhibiting the IL-6/JAK/STAT3 signaling pathway. Consequently, this study demonstrates that JLJG prevents the postoperative recurrence of CRA by inhibiting the IL-6/JAK/STAT3 signaling pathway and its negative feedback loops.