Effects of combined OncoTherad immunotherapy and probiotic supplementation on modulating the chronic inflammatory process in colorectal carcinogenesis

Author(s)

Reis, Sabrina Karen ; Rabelo Socca, Eduardo Augusto ; de Souza, Bianca Ribeiro ; Genaro, Sandra Cristina ; Duran, Nelson ; Favaro, Wagner Jose

• Document type: Journal article
• Source: TISSUE & CELL; v. 75, p. 13-pg., 2022-04-01.

Abstract

This study evaluated the effects of combined OncoTherad immunotherapy and probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) in mice. The animals were randomly allocated in five groups: Control, DMH: did not receive any treatment; DMH + OncoTherad: received weekly I.P. (intraperitoneal) dose of OncoTherad; DMH + Probiotic: received daily administrations via gavage of the functional food (Lactobacillus: acidophilus and paracasei, Bifidobacterium: lactis and bifidum) and DMH + Probiotic + OncoTherad: received the same treatment than the previous groups. After ten weeks of treatment, the large intestine was collected for immunohistochemical analysis of TLR4, MyD88, NF-kappa B, IL-6, TLR2, TRIF, IRF-3, IFN-gamma, Ki-67, KRAS, IL-10, and TGF-beta. For the statistical analysis, the variance tests (ANOVA) and Kruskal-Wallis were used and significance set at p < 0.05. Probiotic supplementation associated with the OncoTherad were able to modulate weight loss, stimulate the canonical signaling pathway TLR2/TLR4 (MyD88-dependent), reduce the non-canonical signaling pathway (TRIF-dependent), attenuate the proliferative pathway mediated by Ki-67 and KRAS oncogene, and stimulate the production of IL-10 and TGF-beta cytokines. Thus, the association of OncoTherad and probiotic supplementation has shown important immudomulatory effects and could be considered a potential new therapeutic approach for colorectal cancer after further investigations. (AU)

• FAPESP's process: 20/03419-6 - Therapeutic and toxicological effects of OncoTherad (MRB-CFI-1) immunotherapy in patients with BCG-refractory or relapsed non-muscle invasive bladder cancer
• Grantee: Wagner José Fávaro
• Support Opportunities: Regular Research Grants