Page 93 - SDIR5 Abstract book 21 12 2021.

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

2
2
2
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
6
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)].

80