Modulation of transforming growth factor beta2 (TGF-beta2) by inositol hexaphosphate in colon carcinogenesis in rats<A NAME="volta1"></A>

Abstract

Modulation of transforming growth factor beta2 (TGF-beta2) by inositol hexaphosphate in colon carcinogenesis in rats Modulation of transforming growth factor beta2 (TGF-beta2) by inositol hexaphosphate in colon carcinogenesis in rats 1 Modulação do fator transformador de crescimento beta2 (TGFbeta2) pelo inositol hexafosfato na carcinogênese colônica em ratos ABSTRACT Purpose: To evaluate modulation in the expression of Transforming growth factor beta2 (TGF-beta2) in short-term colon carcinogenesis. Methods: 64 male rats was used, comprising 4 groups of 16 animals each: group 1 received Inositol hexaphosphate (IP6) and azoxymethane (AOM); group 2, AOM alone; group 3, IP6 alone; group 4 was used as control. Groups 1 and 3 were given 1% IP6 in drinking water for 6 weeks. AOM was administered subcutaneously at weeks 3 and 4 of the experiment at 20 mg/kg of body weight each week. Immunohistochemical processing was performed with the use of anti-TGF-beta2 primary antibodies in right colon samples and quantitation of TGF-beta2 as percentage of expression, through computer-assisted image processing. Results: mean values of TGF-beta2 expression were 9.0 ± 3.9% for group 4 (control), 12.7 ± 4.0% for group 3 (IP6), 19.3 ± 6.2% for group 2 (AOM), and 13.1 ± 5.3% for group 1 (IP6+AOM). The value of p was calculated as 0.0001 for a 5% or lower significance level. Conclusion: the experiment revealed a significant increase in TGF-beta2 expression in right colon with the administration of AOM, and a significant decrease in TGF-beta2 expression when IP6 was administered with AOM. Keywords: Transforming Growth Factor Beta. Phytic Acid, Azoxymethane. Rats. RESUMOObjetivo: Avaliar a modulação da expressão do TGF-beta2 na carcinogênese colônica de curta duração em colon direito de ratos. Método: foram utilizados 64 ratos Wistar, machos divididos em 4 grupos de 16 animais. Grupo 1: recebeu Inositol hexafosfato (IP6) e azoximetano (AOM). Grupo 2 recebeu somente AOM. Grupo 3: recebeu somente IP6. Grupo 4: grupo de controle não recebeu nem IP6 nem AOM. O azoximetano (AOM) foi ministrado na dose 20mg/kg, por via subcutânea na 3ª e 4ª semanas do experimento. Foi realizada imunoistoquímica utilizando-se anticorpo primário TGFbeta2. Utilizou-se processamento de imagem computadorizada para quantificação da expressão do TGFbeta2. Resultados: a média da expressão do TGFbeta2 foi de 9.0 ± 3.9% para o grupo 4 (controle), 12.7 ± 4.0% para o grupo 3 (IP6), 19.3 ± 6.2% para o grupo 2 (AOM), e 13.1 ± 5.3% para o grupo 1 (IP6+AOM). Conclusão: ocorreu aumento significante a da expressão de TGF-beta2 no cólon, com a administração de AOM, e uma diminuição significante na expressão de TGF-beta2 quando IP6 IP6 foi administrado com AOM. Descritores: Fator Transformador de Crescimento Beta. Ácido Phytico acid, Azoximetano. Ratos. -ORIGINAL ARTICLE

Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice

“…VEGF and bFGF bind to their receptors on cell membranes to perform their biological functions, including roles in the Ras/Raf/MAPK [ 58 ], PI3K/Akt [ 59 ] and PI3K/PKC pathways [ 60 ], to promote vascular endothelial cell growth and increase vascular permeability. Marks et al have revealed that TGF-β is highly expressed in CRC tissues induced by azoxymethane (AOM) and that IP6 intervention significantly reduces TGF-β expression [ 61 ]. TGF-β promotes the development of tumor angiogenesis, which is related to the TGF-β/Smad signal transduction pathway, as well as alternative pathways (e.g., the MAPK, PI3K/AKT, and NF-κB pathways) [ 62 , 63 , 64 ].…”

Cellular and molecular maturation in fetal and adult ovine calcaneal tendons

“…), quantified to evaluate cell proliferation; TGF‐β1 expression (TGFβ, positive area in μm 2 in the field; Marks et al. ), to measure the ECM remodeling key factor; neurofilament 200 (NF200) expression (NF200, positive area in μm 2 in the field; Ferreira‐Gomes et al. ; Chen et al.…”

“…Barboni et al 2012b). Guided programs (macros for KS300) were created to count internally a standard field of 15 000 lm 2 : 1 cellularity (total number of DAPI-stained nuclei in the field; Martelli et al 2009;Barboni et al 2012b); 2 proliferation index (PI; % Ki-67 green-stained cells/total number of nuclei in the field; Martelli et al 2009;Barboni et al 2012b), quantified to evaluate cell proliferation; 3 TGF-b1 expression (TGFb, positive area in lm 2 in the field; Marks et al 2006), to measure the ECM remodeling key factor; 4 neurofilament 200 (NF200) expression (NF200, positive area in lm 2 in the field; Ferreira-Gomes et al 2010 ;Chen et al 2013) to evaluate tendon innervation; 5 nerve growth factor (NGF) expression (NGF, positive area in lm 2 in the field; Fressinaud et al 2003), to measure the key molecule for nerve growth and maintenance; 6 vascular area (VA, vWF-positive area in lm 2 in the field; Martelli et al 2009;Barboni et al 2012b), to evaluate blood vessel organisation; 7 VEGF expression (VEGF, positive area in lm 2 in the field; Maae et al 2011), to measure the key molecule for blood vessel remodeling.…”

The role of Fas ligand protein in the oxidative stress induced by azoxymethane on crypt colon of rats

“…In previous reports we demonstrated the association of AOM and the occurrence of ACF in a rat model. In this research we used the similar model to induce the oxidative stress [13][14][15] .…”