Page 92 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

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Inhibition of cancer growth with NF-kB suppressor nitroglycerin can be reversed by NF-kB
stimulation in hamster fibrosarcoma

Dušica, J. Popović , Dušan Lalošević ,Kosta J. Popović , Dejan Miljković ,
1
1
2
1
1
3
Jovan K. Popović , Ivan Čapo
1 Department of Histology and Embriology, Faculty of Medicine, University of Novi Sad,
Hajduk Veljkova 3, 21137 Novi Sad, Republic of Serbia
2 Department of Pharmacy, 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 possible role of the NF-kB in the anticancer effect of nitroglycerin with
metformin on experimental BHK-21/C13-induced fibrosarcoma in hamsters. Material and Methods: Peroral
treatment of tumor-bearing hamsters carried out with a pure combination of NF-kB suppressors
nitroglycerin 25 mg/kg and metformin 500 mg/kg daily and with additional rescue doses of NF-kB stimulator
mebendazole 460 mg/kg daily, via a gastric probe after tumor inoculation. After animal sacrification, 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 for proliferation marker protein Ki-67, proliferating cell nuclear antigen
PCNA, hematopoietic progenitor cell antigen CD34, cluster of differentiation 31 (CD31), cytochrome c
oxidase subunit 4 (COX4), mitochondria marker Cytochrome C, glucose transporter 1 (GLUT1) and inducible
nitric oxide synthase (iNOS), and the main organs were toxicologically tested. The Ki-67 and PCNA positivity
and the cytoplasmic marker (CD34, CD31, COX4, Cytochrome C, GLUT1, iNOS) immunoexpression in the
tumor samples were quantified. Results: The combination of NF-kB suppressors nitroglycerin and
metformin significantly inhibited fibrosarcoma growth in hamsters without toxicity, compared to control.
Co-treatment with NF-kB stimulator mebendazole inhibited anticancer activity of the NF-kB suppressors
nitroglycerin and metformin combination. NF-kB stimulator mebendazole rescued tumor progression
inhibited by the NF-kB suppressors nitroglycerin and metformin. Conclusion: Anticancer effect of
nitroglycerin with metformin might be through NF-kB suppression and might be an effective and safe
approach in novel nontoxic adjuvant and relapse prevention oncological treatment.
Keywords: nitroglycerin, metformin, mebendazole, hamsters, BHK-21/C13, 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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