Paradoxical Regulation of α7nAChR and NLRP3 Inflammasome in Gastrointestinal Cancers and Ulcerative Colitis

Background: Gastrointestinal (GI) cancers are common and pose a major public health issue. An inflammatory microenvironment drives their development and progression. The α7nAChR receptor, known to suppress autoimmune and inflammatory bowel diseases, is also linked to colorectal cancer. It enhances anti-inflammatory activity, influences tumor growth, metastasis, and treatment response, and is associated with tobacco use. NLRP3, a key inflammatory mediator, connects immunity and cancer. The α7nAChR receptor modulates tumorigenesis and therapy response by suppressing inflammatory pathways, while also regulating NLRP3 inflammasome activation through inhibition of mitochondrial DNA release. This study examines α7nAChR and NLRP3 expression in gastric and colorectal cancers, colitis, and normal tissues to clarify pathogenic mechanisms and identify therapeutic targets. Methods: Tissue samples of gastric tumor (S-Tm) (n = 10), colorectal tumor (C-Tm) (n = 10), colitis (UC) (n = 10), healthy stomach (S-C) (n = 10) and healthy colorectal tissue (C-C) (n = 10) taken during routine endoscopy protocols were homogenized. The α7nAChR and NLRP3 levels were examined using the ELISA method, and groups were compared. Results: We identified statistically significant differences in α7nAChR levels between the S-C and S-Tm (p < 0.05), C-C and C-Tm (p < 0.05), and S-C and C-Tm (p < 0.001) groups. The NRLP3 levels also differed significantly between the UC and C-Tm (p < 0.05), the S-C and C-Tm (p < 0.01), and the C-C and C-Tm groups (p < 0.01). Conclusions: Paradoxically, given the inflammatory regulatory role and oncogenic effects of α7nAChR, the relationship between α7nAChR and NLRP3 has become an important target for both oncological and inflammatory therapeutic approaches, particularly in inflammation-related GI cancers.