The role of TNF-α and NFkβ in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine

TNF-α 和 NFkβ 在 1,2-二甲基肼肠癌实验模型中的作用

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作者:Márcio Alencar Barreira, Márcio Wilker Soares Campelo, Conceição da Silva Martins Rebouças, Ana Paula Bomfim Soares Campelo, Paulo Roberto Leitão de Vasconcelos

Conclusions

Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

Methods

Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis' test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney's test was used. P < 0.05 was considered significant.

Purpose

To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH).

Results

The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group. Conclusions: Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

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