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All Journal Biomedical Journal of Indonesia Jurnal Ilmiah Universitas Batanghari Jambi Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research Jurnal Kesehatan Masyarakat Indonesia (JKMI)
Avit Suchitra
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Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Civil Engineering, Building, Construction & Architecture Dentistry Economics, Econometrics & Finance Education Health Professions Immunology & microbiology Law, Crime, Criminology & Criminal Justice Medicine & Pharmacology Neuroscience Nursing Public Health Veterinary

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Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model Arli Suryawinata; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra; Raflis Rustam
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1572

Abstract

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties. Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR. Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094). Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.
Co-Authors Aini, Julpa Nurul Arli Suryawinata Aswiyanti Asri Dally Rahman Darmawidyawati Darmawidyawati Dina Arfiani Rusjdi Emil Huriani Fachry Abda El Rahman Fitri Nur Handriyani Hafizah Putri Tasyah Henny Mulyani Husna Yetti Irwan Leonard Khriestsandi Saleh Loli Devianti M Iqbal Rivai M. Iqbal Rivai Novita Ariani Noza Hilbertina Oktarina, Elvi Raflis Rustam Ramata, Yudi Ichsan Rina Gustia Susmiati Susmiati Suswita, Rini Tofrizal