Satuman (2021) Mekanisme Stimulasi Kanker Oleh Protein Efektor Avra Salmonella Typhimurium Pada Kanker Kolon. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Background: One of the risk faktors for colorectal cancer is Salmonella bacterial infection. Salmonella typhimurium is a Gram-negative bacterium that is able to trigger cross infection between humans and animals. This bacterium possibly becomes the risk faktor for colorectal cancer. Salmonella and its effector, AvrA, are able to convert stem cells into cancer stem cells through changes in the microenvironment by suppressing the immune system, increasing inflammation and radical oxygen species (ROS). AvrA effector may be able to disrupt PTEN signals and regulatory T cells and affect c-Myc as a proto-oncogene of malignancy. Purpose: The aim of this study was to explain the mechanism of AvrA and Salmonella typhimurium infection as risk faktors for colorectal cancer by observing AvrA bonds in the colon, AvrA expression, activation of regulator T cells, IFN-γ level, the number of intracellular ROS and cancer stem cells, PTEN expression and its c-myc in mice model of colorectal cancer induced with axozymethane. Methods: This was a faktorial experimental research. This research used Balb/c mice model of colorectal cancer with azoxymethane induction and they were given AvrA and infected with Salmonella typhimurium in vivo. The AvrA was isolated from Salmonella typhimurium protein. Testing of AvrA bonds with receptors or chemokines was done by docking using CLUSPRO 2.2 software. The amount of forty mice were divided into several groups which were control group, group given azoxymethane (AOM) only, group given AOM + AvrA, and group given AOM + S. typhimurium. The mice were killed after 1st week and 12th weeks of treatment. AvrA, PTEN and c-Myc expressions were analysed with immunohistochemistry method, regulator T cells, ROS and the colon cancer stem cell numbers were analysed with flow cytometry method, and IFN-γ levels were analysed with ELISA method. The Statistical analysis were analysed with Kruskal Wallis and Mann Whitney and followed by Path analysis. Results: AvrA Salmonella typhimurium penetrated the colon cells by binding to CXCR3. This study found significant differences in AvrA expression, regulatory T cells, IFN-γ levels, intracellular ROS amount, colon cancer stem cells, PTEN expression, c-Myc expression in each group in 1st week and 12th weeks. Conclusion: AvrA Salmonella typhimurium was able to induce colorectal cancer.

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