en Blood and Immune System Blood and Immune System Experimental research article Experimental research article <p><strong>Introduction:</strong> Lactic acid bacteria, recognized as probiotics, have garnered significant attention as potential adjuvants in chemotherapy for various cancer types, including cervical cancer. In this study, we investigated the anti-cancer properties of two indigenous Iranian strains, Lactobacillus acidophilus and Lactobacillus paracasei, individually and in combination, targeting human cervical cancer cell lines compared to normal control cells.<br /> <strong>Methods:</strong> The cytotoxic effect of Lactobacillus acidophilus and Lactobacillus paracasei supernatants, as well as their 1:1 mixture, on CaSki and HNCF PI 52 cell lines, was evaluated using the MTT assay. The apoptotic and anti-metastatic effects of these supernatants were assessed by analyzing the gene expression of BAX/BCL2 ratio, Caspase-3, and MMP2/ MMP9 using Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).<br /> <strong>Results: </strong>Significant cytotoxicity was observed in Ca Ski cells attributed to the low pH of the supernatants. The increase in the BAX/BCL2 ratio, leading to an up-regulation of Caspase-3, indicated the induction of apoptosis (P<0.001). In addition, the expression of MMP9 significantly deceased in Ca Ski cells treated with Lactobacillus acidophilus (P<0.001) and Lactobacillus paracasei (P<0.05), while no significant difference in MMP2 expression was observed in all samples compared to the control groups.<br /> <strong>Conclusion: </strong>while further validation is needed, the heightened expression of apoptotic genes suggests a potential induction of apoptosis in cancer cells in response to Lactobacillus toxicity. The significant down-regulation of the MMP9 gene emphasizes the need for comparative analyses across different cervical cancer cell lines to establish the anti-metastatic potential of these local probiotic supernatants.</p> Cervical cancer, Lactobacillus acidophilus, Lactobacillus paracasei, Probiotics 426 434 http://ppj.phypha.ir/browse.php?a_code=A-10-1668-1&slc_lang=en&sid=1 Iman Samiei Mosleh imansamiemosleh@gmail.com 3200319475328460034219 3200319475328460034219 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Fatemeh Karami Fatemeh.karami@srbiau.ac.ir 3200319475328460034220 3200319475328460034220 Yes Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran Iman Salahshourifar isalahshouri@gmail.com 3200319475328460034221 3200319475328460034221 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Maryam Tajabadi Ebrahimi ebrahimi_mt@yahoo.com 3200319475328460034222 3200319475328460034222 No Department of Biology Central Tehran Branch Islamic Azad University Tehran Iran Mohsen Marvibaigi 3200319475328460034223 3200319475328460034223 No 4 Department Biology, Kavian Institute of higher education, Mashhad, Iran