INTERNATIONAL CONGRESS OF
CancerGenetics
Exploring the Anti-Cancer Potential of Probiotics: EGFR Pathway Modulation in Colorectal Cancer
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Mona Arefi,1,*
1. faculty of advanced science and technology, Tehran medical science, Islamic Azad University, Tehran, Iran
- Introduction: The epidermal growth factor receptor (EGFR) pathway plays a crucial role in colorectal cancer (CRC) and can be affected by specific probiotics. The EGFR family consists of four members: EGFR/ErbB1, HER1, HER2/ErbB2/Neu, HER3/ErbB3, and HER4/ErbB4. When ligands bind to these receptors, they dimerize, activating their tyrosine kinase domains, which triggers various cell responses, such as growth and differentiation. In the context of CRC, the overexpression of EGFR and HER2 interferes with this pathway, leading to heightened cell growth, survival, and the potential for metastasis. As a result, both EGFR and HER2 have become important targets for treatment, with cetuximab and trastuzumab being among the available therapies.
- Methods: The anticancer effects of potential probiotic groups were examined in LS174T cancer cells compared to IEC-18 normal cells. The groups included: 1. a single strain of Bifidobacterium breve, 2. a single strain of Lactobacillus reuteri, 3. a cocktail of 5 Lactobacillus strains (LC), 4. a cocktail of 5 Bifidobacteria strains (BC), and 5. a cocktail of 10 strains combining Lactobacillus and Bifidobacterium (L+B). Apoptosis rates and expression levels of EGFR, HER-2, and PTGS-2 (COX-2 protein) were measured to evaluate anticancer properties. The BC group, identified as the most effective in vitro, was further tested in mouse models.
- Results: BC induced approximately 21% apoptosis in LS174T cells, while only about 3% in IEC-18 cells. BC reduced the expression of EGFR by 4.4 times, HER-2 by 6.7 times, and PTGS-2 by 20 times in LS174T cells. In contrast, BC had minimal impact on gene expression in IEC-18 cells, resulting in only a 1.1-fold decrease, a 1.8-fold increase, and a 1.7-fold decrease in EGFR, HER-2, and PTGS-2 expression, respectively. Western blot analysis corroborated these findings at the protein level. Additionally, BC significantly improved the disease activity index, restored colon length, and prevented the increase in tumor incidence and progression to more advanced stages and grades.
- Conclusion: Overall, taking into account the impact on both cancer and normal cell lines, the Bifidobacteria cocktail proves to be the most effective treatment compared to the other bacterial combinations tested in this study. This promising probiotic demonstrates significant “protective” anti-cancer effects similar to the established drugs cetuximab and trastuzumab, capable of downregulating onco-markers such as EGFR, HER-2, and PTGS-2 (COX-2). It notably improves the disease activity index, restores colon length, reduces tumor incidence, and prevents tumors from advancing to more severe stages. In general, this probiotic could be a beneficial nutritional supplement to use alongside cetuximab and trastuzumab for treating and preventing colorectal cancer (CRC). As the findings of this study may vary by strain and cell type, further research on different Bifidobacterial strains and cell types is advisable to gain a deeper understanding of this bacterium’s anti-CRC mechanisms.
- Keywords: Colorectal Cancer, EGFR Pathway, Probiotics, HER-2
