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INTERNATIONAL CONGRESS OF

CancerGenetics

• The Synergistic Effects of Cisplatin and Probiotics on BAX and Bcl-2 Gene Expression in Breast Cancer Cells

• Farzin Javid,^1,* Javad Allahverdy,²
  1. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
  2. Laboratory Sciences Department, Faculty of Allied Medicine, Iran University of Medical Sciences
  
  
  
• Introduction: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Despite advances in treatment, the resistance of cancer cells to chemotherapeutic agents such as cisplatin remains a significant challenge. Cisplatin is a widely used chemotherapy drug that induces apoptosis by forming DNA adducts and activating apoptotic pathways. However, breast cancer cells can develop resistance to cisplatin, limiting its therapeutic effectiveness. Recent studies have suggested that probiotics, particularly strains of "Lactobacillus" and "Bifidobacterium", could improve chemotherapy outcomes by modulating the gut microbiota and immune responses, as well as by enhancing apoptotic signaling pathways in cancer cells. This review focuses on the combined use of cisplatin and probiotics in breast cancer treatment and their effects on the expression of "Bax" and "Bcl-2", two critical genes involved in apoptosis regulation.
• Methods: This review examines recent studies from the last five years that have investigated the effects of cisplatin and probiotics on breast cancer cells. A literature search was conducted using databases such as PubMed and Google Scholar, with a focus on studies that assessed the apoptotic response in breast cancer cells treated with both cisplatin and probiotics. Studies analyzing the expression of pro-apoptotic "Bax" and anti-apoptotic "Bcl-2 genes were selected. The included research covered in vitro experiments on breast cancer cell lines, particularly MCF-7 cells, as well as in vivo studies on animal models.
• Results: The combined treatment of cisplatin and probiotics demonstrated significant effects on the expression of "Bax" and "Bcl-2" in breast cancer cells. Cisplatin alone is known to induce apoptosis through the upregulation of "Bax" and downregulation of "Bcl-2", tipping the balance toward cell death. In several studies, probiotics, especially strains like "Lactobacillus rhamnosus" and "Bifidobacterium bifidum", enhanced this effect. In vitro studies on MCF-7 breast cancer cells showed that treatment with cisplatin led to a 2.5-fold increase in "Bax" expression and a 35% reduction in "Bcl-2" levels. When combined with probiotics, "Bax" expression increased up to 4-fold, while "Bcl-2" levels decreased by 60%, indicating a synergistic effect. This shift in the *Bax/Bcl-2* ratio promotes apoptosis, as "Bax" facilitates mitochondrial membrane permeabilization, releasing cytochrome c and activating caspases, while "Bcl-2" acts to inhibit these processes. Further studies demonstrated that probiotics not only enhanced the pro-apoptotic effects of cisplatin but also contributed to reducing inflammation and improving the overall immune response. By modulating the gut microbiome, probiotics may promote systemic immune responses, which could help in identifying and targeting cancer cells more effectively. Animal models of breast cancer corroborated these findings. Mice treated with both cisplatin and probiotics showed a significant reduction in tumor size compared to those treated with cisplatin alone. Tumor tissues from these mice exhibited higher levels of "Bax" and lower levels of "Bcl-2", further confirming the apoptotic effect of the combined treatment.
• Conclusion: The combination of cisplatin and probiotics offers a promising strategy for enhancing the effectiveness of breast cancer treatment. By modulating the expression of key apoptotic genes such as "Bax" and "Bcl-2", probiotics help to amplify the pro-apoptotic effects of cisplatin, making cancer cells more susceptible to programmed cell death. These findings suggest that probiotics may serve as a valuable adjunct to traditional chemotherapy, potentially overcoming resistance mechanisms and improving patient outcomes. Future clinical trials are necessary to establish the optimal combination of probiotics and chemotherapy drugs, as well as to confirm these findings in a clinical setting.
• Keywords: Probiotic, apoptosis, Bcl-2, bax, breast cancer