Popović, Kosta J. Popović, Dušica J. Miljković, Dejan Lalošević, Dušan Čapo, Ivan Poša, Mihalj Dolićanin, Zana Popović, Jovan K. info:eu-repo/semantics/conferenceProceedings All rights reserved 2023 application/pdf 397039 bytes Serbian Society for Molecular Biology, CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, 06-08 October 2023, Belgrade, Serbia. Abstract Book – Trends in Molecular Biology, Special issue(2) Rescuing hamster fibrosarcoma growth by stimulation of different prooncogenic signaling pathways relative to repurposed anticancer drug mechanisms eng Keywords : fibrosarcoma; hamster; repurposed drugs; anticancer mechanism. https://phaidrabg.bg.ac.rs/o:31328 Abstract: Many drugs registered for various non-oncological indications influence tumor metabolic processes, signaling pathways, enzymes, proteins, tumor receptors and genes that regulate proliferation, neoangiogenesis, apoptosis and necroptosis, without affecting these activities in healthy cells. The aim: Detecting underlying anticancer mechanism of metformin in two-drug combinations with other repurposed drugs (2-Deoxy-D-glucose, deoxycholic acid, caffeine, itraconazole or disulfiram) by rescuing BHK-21/C13 hamster fibrosarcoma growth with glucose, vitamin C, nitroglycerin or mebendazole. Methods: The anticancer mechanisms of examined drug combinations, <50% LD50 (equivalent to usual human dose), were determined by rescuing fibrosarcoma growth with addition of aforementioned agents in treatment. Immunohistochemical markers (Ki-67, PCNA, CD34, CD31, GLUT1, iNOS, COX4, Cytochrome C) in control and experimental groups were assessed 19 days after BHK-21/C13 tumor inoculation. Tumors were excised, measured and blood collected. Biophysical, pathohistological, toxicological, hematological, biochemical and statistical analyses were performed. Results: Only addition of NF-kB stimulator mebendazole to effective two-drug combinations containing metformin rescued cancer growth, indicating that this pathway may be responsible for antitumor action. Conclusion: NF-kB signaling pathway downregulation plays an essential role among anticancer mechanisms of investigated metformin combinations in hamster fibrosarcoma treatment.