Modulated Hepatic Expression of NF-kB and CCN1 Genes in a Breast Cancer Mouse Model Induced by DMBA and High-Fat Diet

Authors

  • Demes Chornelia Martantiningtyas Department of Biochemistry, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia
  • Raden Ghita Sariwidyantry Department of Biochemistry, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia
  • Hana Ratnawati Department of Histology, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia
  • Teresa Lilliana Wargasetya Department of Pathology, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia
  • Ardo Sanjaya Department of Anatomy, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia

DOI:

https://doi.org/10.30742/jikw.v14i1.4002

Keywords:

DMBA, high-fat diet, NF-κB, CCN1/CYR61, hepatic gene expression, breast cancer, inflammation, fibrosis

Abstract

Background: The study investigates the combined effects of 7,12-dimethylbenz[a]anthracene (DMBA) and a high-fat diet (HFD) on hepatic gene expression in a breast cancer mouse model. Both DMBA and HFD are associated with oxidative stress, inflammation, and fibrosis, which may contribute to cancer progression.

Methods: Female C57BL/6 mice were divided into three groups: standard diet (ND), ND + DMBA, and HFD + DMBA. Mice in the ND + DMBA and HFD + DMBA groups received DMBA injections weekly for six weeks. The HFD + DMBA group was also fed a high-fat diet for four weeks prior to DMBA administration. After a 12-week treatment period, liver tissues were collected and analyzed for NF-κB and CCN1/CYR61 gene expression using semi-quantitative RT-PCR.

Results: The study revealed significant upregulation of NF-κB and CCN1/CYR61 expression in the ND + DMBA and HFD + DMBA groups compared to the control group. Notably, the HFD + DMBA group exhibited the highest expression levels of these genes, suggesting that the combination of HFD and DMBA synergistically exacerbates hepatic inflammation and fibrosis.

Conclusion: The findings indicate that a high-fat diet in combination with carcinogen exposure can significantly enhance hepatic gene expression related to inflammation and fibrosis, highlighting the importance of dietary management in cancer prevention and treatment.

 

References

Fisher, R., Taha, D. I., & Capes, J. (2016). Role of liver inflammation and fibrosis in cancer metastasis. Journal of Hepatology, 64(2), 404-414. https://doi.org/10.1016/j.jhep.2015.09.023

Friedman, S. L., Ratziu, V., & Harrison, S. A. (2018). Non-alcoholic fatty liver disease: A review of the current understanding and therapeutic options. Gastroenterology, 154(6), 1551-1568. https://doi.org/10.1053/j.gastro.2018.02.009

Gilmore, T. D., & Garbati, M. R. (2011). Inhibitors of NF-kappaB signaling: A review of their effects in cancer. Clinical Cancer Research, 17(1), 11-19. https://doi.org/10.1158/1078-0432.CCR-10-1605

Gao, B., & Bataller, R. (2011). Alcoholic liver disease: Pathogenesis and new therapeutic targets. Gastroenterology, 141(5), 1572-1585. https://doi.org/10.1053/j.gastro.2011.09.021

Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Carcinogenesis initiated and driven by inflammation. Journal of Clinical Investigation, 120(1), 1-9. https://doi.org/10.1172/JCI41388

Jun, J. I., & Lau, L. F. (2018). CCN1/CYR61 in fibrotic disease: A matrix protein with many functions. Matrix Biology, 68-69, 333-345. https://doi.org/10.1016/j.matbio.2018.01.005

Kociba, R. J., & Schwetz, B. A. (2018). Carcinogenicity studies of 7,12-dimethylbenz[a]anthracene (DMBA). Environmental Health Perspectives, 81, 169-174. https://doi.org/10.1289/ehp.818169

Kim, K. K., Wei, Y., & Willis, B. C. (2021). Hyperoxia-induced NF-kB activation mediates fibrotic response in the lung. Journal of Biological Chemistry, 296, 100419. https://doi.org/10.1074/jbc.RA120.014268

Lau, J., O’Doherty, M. G., & Liu, L. F. (2020). High-fat diet and cancer progression: The role of metabolic inflammation. Journal of Clinical Oncology, 38(15_suppl), e18512-e18512. https://doi.org/10.1200/JCO.2020.38.15_suppl.e18512

Leask, A., & Abraham, D. J. (2016). TGF-beta signaling and the fibrotic response. Journal of Pathology, 232(2), 260-272. https://doi.org/10.1002/path.4501

Lu, P., Weaver, V. M., & Werb, Z. (2012). The extracellular matrix: A dynamic niche in cancer progression. Journal of Cell Biology, 196(3), 395-406. https://doi.org/10.1083/jcb.201108052

Macedo, S. A., Santos, A. M., & Bachega, M. (2017). The role of the liver in cancer progression: Implications for therapy. Hepatology International, 11(1), 135-143. https://doi.org/10.1007/s12072-016-9765-8

Musso, G., Gambino, R., & Cassader, M. (2018). Interactions between liver, fat tissue, and gut microbiota in the development of obesity and nonalcoholic fatty liver disease. Digestive Diseases, 36(4), 298-305. https://doi.org/10.1159/000489088

Nguyen, V. T., Le, Q. V., & Nguyen, T. H. (2021). Dietary fat intake and liver cancer risk: Systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention, 30(1), 32-45. https://doi.org/10.1158/1055-9965.EPI-20-0657

Sanyal, A. J., Mofrad, P., & Contos, M. J. (2018). A prospective study of nonalcoholic fatty liver disease in patients with obesity and type 2 diabetes. Gastroenterology, 154(3), 783-793. https://doi.org/10.1053/j.gastro.2017.10.038

Siegel, R. L., Miller, K. D., & Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), 17-48. https://doi.org/10.3322/caac.21763

Sun, S. C., & Karin, M. (2019). NF-kB signaling, vertebrate development and disease. Cell Research, 29(6), 115-135. https://doi.org/10.1038/s41422-019-0154-0

Tsuchida, T., & Friedman, S. L. (2017). Mechanisms of liver fibrosis and its role in hepatocellular carcinoma. Nature Reviews Gastroenterology & Hepatology, 14(5), 254-266. https://doi.org/10.1038/nrgastro.2017.18

Zhou, Y., Liu, M., & Zhang, H. (2020). The role of CCN1 in liver fibrosis: A review. International Journal of Molecular Sciences, 21(3), 782. https://doi.org/10.3390/ijms21030782

Zhu, L., Chen, S., & Zhao, X. (2020). Obesity and the risk of breast cancer: A meta-analysis. Cancer Research, 80(4), 915-926. https://doi.org/10.1158/0008-5472.CAN-19-3346

Downloads

Published

2025-04-11

Issue

Section

Original Research Articles