Page 93 - SDIR5 Abstract book 21 12 2021.
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POSTER PRESENTATIONS



               P53


                  NF-kB inactivation is important for disulfiram suppression of fibrosarcoma which can be
                                rescued by NF-kB stimulator mebendazole in hamster model

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                                            1
                              Kosta J. Popović , Dušica, J. Popović , Dušan Lalošević ,Dejan Miljković ,
                                                                3*
                                                                           2
                                                 Jovan K. Popović , Ivan Čapo
                          1 Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3,
                                                21137 Novi Sad, Republic of Serbia
                           2 Department of Histology and Embriology, Faculty of Medicine, University of Novi Sad,
                                        Hajduk Veljkova 3, 21137 Novi Sad, Republic of Serbia
                3* Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad,
                                        Hajduk Veljkova 3, 21137 Novi Sad, Republic of Serbia

               Background: We investigated involvement of NF-kB in the anticancer effect of disulfiram and metformin
               combination on fibrosarcoma in hamsters. Material and Methods: Hamsters (both sexes; ~ 70 g) were
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               randomly allocated to control and experimental groups (8 animals per group). In all groups, 2 x 10  BHK-
               21/C13 cells in 1 ml were injected subcutaneously into the animals’ backs. Peroral treatments were carried
               out with combination of NF-kB suppressors disulfiram (50 mg/kg/day) and metformin (500 mg/kg/day) and
               by the combination with addition of rescue daily doses of NF-κB stimulator mebendazole 460 mg/kg, via a
               gastric  probe  after  tumor  inoculation.  After  19  days  all  animals  were  sacrificed.  Blood  samples  were
               collected for hematological and biochemical analyses, the tumors were excised and weighed, and their
               diameters  and  volumes  were  measured.  The  tumor  samples  were  pathohistologically  and
               immunohistochemically assessed (Ki-67, PCNA, CD34, CD31, COX4, Cytochrome C, GLUT1, iNOS), and the
               main organs were toxicologically tested. Results: The combination of NF-kB suppressors disulfiram and
               metformin significantly inhibited fibrosarcoma growth in hamsters without toxicity, compared to control.
               Co-treatment  with NF-kB  stimulator mebendazole  completely  blocked  anticancer  activity  of  the  NF-kB
               suppressors  disulfiram  and  metformin  combination,  most  likely  by  NF-κB  stimulation.  Conclusion:
               Anticancer effect of the combination of NF-kB suppressors disulfiram and metformin may be through NF-
               kB suppression and the combination may be used as an effective and safe candidate for novel nontoxic
               adjuvant and relapse prevention oncological therapy.
               Keywords: disulfiram; metformin; mebendazole; hamsters; fibrosarcoma
               Acknowledgements: This study was supported by the Republic of Serbia, Autonomous Province of Vojvodina,
               Provincial Secretariat for High Education and Scientific Research [Project title: Discovery of effective non-
               toxic  anticancer  drug  combinations  on  experimental  fibrosarcomas,  grant  no.  142-451-2498/2021-03
               (Project leader Dušica Popović)] and Republic of Serbia, Ministry of Science [grant no. 172013 (DM)].






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