The Role of TNF-α and NFkβ in an Experimental Model of Intestinal Carcinogenesis with 1,2-dimethyhydrazine

Overview

Journal Acta Cir Bras

Specialty General Surgery

Date 2023 Sep 20

PMID 37729351

Authors

Marcio Alencar Barreira

Marcio Wilker Soares Campelo

Conceicao da Silva Martins Reboucas

Ana Paula Bomfim Soares Campelo

Paulo Roberto Leitao de Vasconcelos

Affiliations

Soon will be listed here.

Abstract

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).

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.

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.

References

El-Khadragy M, Nabil H, Hassan B, Tohamy A, Waaer H, Yehia H . Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats. Cell Physiol Biochem. 2018; 45(3):1072-1083. DOI: 10.1159/000487349. View

Pretlow T, ORiordan M, Pretlow T, Stellato T . Aberrant crypts in human colonic mucosa: putative preneoplastic lesions. J Cell Biochem Suppl. 1992; 16G:55-62. DOI: 10.1002/jcb.240501111. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Wargovich M, Brown V, Morris J . Aberrant crypt foci: the case for inclusion as a biomarker for colon cancer. Cancers (Basel). 2013; 2(3):1705-16. PMC: 3837333. DOI: 10.3390/cancers2031705. View

Brey E, Lalani Z, Johnston C, Wong M, McIntire L, Duke P . Automated selection of DAB-labeled tissue for immunohistochemical quantification. J Histochem Cytochem. 2003; 51(5):575-84. DOI: 10.1177/002215540305100503. View

Bird R, GOOD C . The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett. 2000; 112-113:395-402. DOI: 10.1016/s0378-4274(99)00261-1. View

Pierre C, Longo J, Mavor M, Milosavljevic S, Chaudhary R, Gilbreath E . Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice. Biochim Biophys Acta. 2015; 1852(9):1846-55. DOI: 10.1016/j.bbadis.2015.06.011. View

Hsu S, RAINE L, FANGER H . Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981; 29(4):577-80. DOI: 10.1177/29.4.6166661. View

Jang D, Lee A, Shin H, Song H, Park J, Kang T . The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int J Mol Sci. 2021; 22(5). PMC: 7962638. DOI: 10.3390/ijms22052719. View

10.

Hussain S, Harris C . Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007; 121(11):2373-80. DOI: 10.1002/ijc.23173. View

11.

Burlamaqui I, Dornelas C, Valenca Junior J, Mota D, Mesquita F, Veras L . Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt formation in rat colonic mucosa. Acta Cir Bras. 2011; 27(1):30-6. DOI: 10.1590/s0102-86502012000100006. View

12.

Sakai E, Takahashi H, Kato S, Uchiyama T, Hosono K, Endo H . Investigation of the prevalence and number of aberrant crypt foci associated with human colorectal neoplasm. Cancer Epidemiol Biomarkers Prev. 2011; 20(9):1918-24. DOI: 10.1158/1055-9965.EPI-11-0104. View

13.

Chaturvedi M, Sung B, Yadav V, Kannappan R, Aggarwal B . NF-κB addiction and its role in cancer: 'one size does not fit all'. Oncogene. 2010; 30(14):1615-30. PMC: 3141287. DOI: 10.1038/onc.2010.566. View

14.

Burlamaqui I, Dornelas C, Escalante R, Mota D, Mesquita F, Carvalho E . Optimization of visibility and quantification of aberrant crypt foci in colonic mucosa in Wistar rats. Acta Cir Bras. 2010; 25(2):148-52. DOI: 10.1590/s0102-86502010000200005. View

15.

Johnson R, Fleet J . Animal models of colorectal cancer. Cancer Metastasis Rev. 2012; 32(1-2):39-61. PMC: 3572245. DOI: 10.1007/s10555-012-9404-6. View

16.

Takayama T, Katsuki S, Takahashi Y, Ohi M, Nojiri S, Sakamaki S . Aberrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med. 1998; 339(18):1277-84. DOI: 10.1056/NEJM199810293391803. View

17.

Braga V, Juanes C, Peres Junior H, Sousa J, Cavalcanti B, Jamacaru F . Gum arabic and red propolis protecteting colorectal preneoplastic lesions in a rat model of azoxymethane1. Acta Cir Bras. 2019; 34(2):e201900207. PMC: 6585917. DOI: 10.1590/s0102-8650201900207. View

18.

Modesto R, Estarreja J, Silva I, Rocha J, Pinto R, Mateus V . Chemically Induced Colitis-Associated Cancer Models in Rodents for Pharmacological Modulation: A Systematic Review. J Clin Med. 2022; 11(10). PMC: 9146029. DOI: 10.3390/jcm11102739. View

19.

Klampfer L . Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets. 2011; 11(4):451-64. PMC: 3540985. DOI: 10.2174/156800911795538066. View

20.

Rudolph R, Dominitz J, Lampe J, Levy L, Qu P, Li S . Risk factors for colorectal cancer in relation to number and size of aberrant crypt foci in humans. Cancer Epidemiol Biomarkers Prev. 2005; 14(3):605-8. DOI: 10.1158/1055-9965.EPI-04-0058. View