AvrA Salmonella Increases TLR4/NF-κB/β-catenin/TGF-β Expressions of Colorectal Cancer Mice Model

Bogi Pratomo Wibowo (Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang 65145)
Handono Kalim (Rheumatology and Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya/Dr. Saiful Anwar General Hospital, Jl. Jaksa Agung Suprapto No. 2, Malang 65112)
Husnul Khotimah (Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang 65145)
Hidayat Sujuti (Department of Biochemistry/Biomolecular, Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang 65145)
Ettie Rukmigarsari (Mathematics Education Study Program, Faculty of Teacher Training and Education, Universitas Islam Malang, Jl. MT. Haryono 193, Malang 65144)
Nabila Erina Erwan (Master in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang 65145)

The Indonesian Biomedical Journal
Vol 15, No 6 (2023)

BACKGROUND: Colorectal cancer (CRC) is reported as the third most frequently diagnosed cancer worldwide. Salmonella infection plays a role in developing this cancer, which is chronically related to the avirulence protein A (AvrA) effector protein produced by the bacteria. This study was conducted to point out the effect of AvrA Salmonella on the occurrence of CRC through the regulation of TLR4/NF-κB/β-catenin/TGF-β expressions in the azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model.METHODS: A randomized control group post-test-only study was conducted using male Balb/c mice with 30-gram body weight (10-12 weeks), which were divided into three groups, namely the negative control (normal mice without any treatment), positive control (AOM/DSS-treated mice), treatment 1 (T1) (AOM/DSS-treated mice + AvrA Salmonella) groups. Colon tissue was collected and then prepared for immunohistochemistry staining using TLR4, β-catenin, NF-κB, TGF-β, and Ki67 antibodies, whereas apoptotic cells were stained using TUNEL assay.RESULTS: The expressions of TLR4, β-catenin, NF-κB, TGF-β, Ki67, and apoptosis percentage indicated significant differences among the three groups, which statistically showed p<0.05 in all observed parameters. The mean of all parameters was far more significant in the T1 group than in the negative and positive control groups.CONCLUSION: The findings revealed that AvrA Salmonella could increase the expressions of TLR4, β-catenin, NF-κB, TGF-β, and Ki67 and decrease the apoptotic percentage. Thus, AvrA Salmonella influences CRC tumorigenesis through TLR4/NF-κB/β-catenin/TGF-β and is suggested as a potential target in future preventive and curative management for CRC.KEYWORDS: AvrA Salmonella, carcinogenesis, colorectal cancer