Resolvin E1 and Maresin 1 Attenuate Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3-Associated Inflammation and Invasion in Oral Squamous Cell Carcinoma.
The American journal of pathology, vol.196, no.8, pp.1777-1802, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 196 Issue: 8
- Publication Date: 2026
- Doi Number: 10.1016/j.ajpath.2026.04.017
- Journal Name: The American journal of pathology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
- Page Numbers: pp.1777-1802
- Bursa Uludag University Affiliated: Yes
Abstract
Inflammation critically contributes to the progression of oral squamous cell carcinoma (OSCC), a common and aggressive oral cancer. Excessive nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome activation drives tumor-associated chronic inflammation, which oral pathogens can trigger to enhance invasion and metastasis. The present study investigated the effects of resolvin E1 (RvE1) and maresin 1 (MaR1) on NLRP3-associated inflammation and evaluated whether promoting inflammation resolution limits tumor aggressiveness in OSCC. RvE1, MaR1, or vehicle was administered in a xenograft OSCC model generated by s.c. injection of MOC2 cells in wild-type C57BL/6 mice. To assess NLRP3's role, an Nlrp3 knockout OSCC model was used in B6.129S6-Nlrp3tm1Bhk/J mice. Both treatments reduced NLRP3 expression, tumor-associated macrophages and neutrophils, and secretion of IL-1β, IL-18, and IL-6 (P < 0.05). RvE1 and MaR1 also suppressed NLRP3 activation in OSCC cells and inhibited macrophage-mediated activation, reducing MOC2-sphere growth, migration, and apoptosis-related caspase activity. In Porphyromonas gingivalis–primed cells treated with nigericin, both specialized proresolving mediators decreased NLRP3 activation (P < 0.05). These findings indicated that RvE1 and MaR1 resolve the inflammatory microenvironment in OSCC, thereby limiting tumor aggressiveness, highlighting their potential as therapeutic strategies to reduce tumor invasion and metastasis.