Synergistic Attenuation of the TNF-α/NF-κB Inflammatory Axis in Colorectal Carcinogenesis: Lactococcus lactis D4 as a Mucosal-Protective Adjuvant to Capecitabine
DOI:
https://doi.org/10.37275/bsm.v10i4.1571Keywords:
Capecitabine, Colorectal cancer, Lactococcus lactis, Synergy, TNF-αAbstract
Background: Capecitabine serves as a standard chemotherapeutic agent for colorectal cancer, but its clinical efficacy is frequently hindered by severe gastrointestinal toxicity and incomplete suppression of the inflammatory tumor microenvironment. We evaluated the synergistic potential of Lactococcus lactis D4, a probiotic strain isolated from traditional fermented buffalo milk, as an immunonutritional adjuvant to Capecitabine in a 1,2-dimethylhydrazine-induced colorectal cancer rat model.
Methods: Sprague-Dawley rats were maintained on a standardized AIN-93G diet and induced with 1,2-dimethylhydrazine. Animals were randomized into Negative Control, Cancer Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Treatments were administered for 14 days. We assessed cachexia, macroscopic microadenoma multiplicity, and TNF-α expression utilizing immunohistochemistry. Synergy was mathematically validated using the Coefficient of Drug Interaction.
Results: The Combination group significantly prevented chemotherapy-induced cachexia, demonstrating a 2.1% weight gain compared to a 4.5% weight loss in the Capecitabine monotherapy group (p < 0.05). Macroscopic microadenomas were rapidly reduced in the combination group. Furthermore, the combination therapy synergistically suppressed colonic TNF-α protein expression (Coefficient of Drug Interaction = 0.83). Additionally, L. lactis D4 entirely mitigated capecitabine-induced mucositis.
Conclusion: L. lactis D4 functions as a highly potent adjuvant to Capecitabine. It prevents cachexia, protects mucosal architecture, and exerts a mathematically proven synergistic suppression of the TNF-α inflammatory axis.
Authors
- Leonard Khriestsandi Saleh1*
- M Iqbal Rivai2
- Rini Suswita2
- Irwan2
- Avit Suchitra2
- 1Department of Surgery, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
- 2Department of Surgery, Division of Digestive Surgery, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
Corresponding author Leonard Khriestsandi Saleh — leonard_khriestsandi@yahoo.com
Article history
- Submitted
- Accepted
- Published
Downloads
Published
Issue
Section
License
Copyright and licensing
Copyright in each article remains with the author(s). Authors grant Bioscientia Medicina: Journal of Biomedicine and Translational Research a non-exclusive right of first publication and the right to identify itself as the original publisher. No exclusive transfer of copyright is required.
All articles are published under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0): https://creativecommons.org/licenses/by-nc-sa/4.0/. Users may copy, redistribute, remix, transform, and build upon the material for non-commercial purposes, provided appropriate attribution is given, a link to the license is supplied, changes are indicated, and adaptations are distributed under the same license.
The license applies to the article's scholarly content unless a credit line states otherwise. Third-party material may be subject to separate rights. Authors retain patent, trademark, moral, and research-data rights. The copyright year follows the article's publication date.
