Abstract
Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC).
The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare.
The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA).
We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa.
The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-α induction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-α expression.
Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-α expression.
Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.
See also:
- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);
- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Oesophageal squamocellular carcinoma: a complete and objective response;
- Complete objective response to biological therapy of plurifocal breast carcinoma.