Effect of metformin on fibrosarcoma in hamsters

D.J. Popović, D. Lalošević, D. Miljković, K.J. Popović, I. Čapo, J.K. Popović

Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Republic of Serbia. jovan.popovic@mf.uns.ac.rs

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• Pharmacology

OBJECTIVE: We investigated the effect of metformin on an in vivo solid tumor model of fibrosarcoma in hamsters.

MATERIALS AND METHODS: 33 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals’ back in 4 groups. The first experimental group (7 animals) started peroral treatment with metformin 500 mg/kg daily via a gastric probe 7 days before tumor inoculation, the second (8 animals) 3 days before inoculation and the third (6 animals) immediately after inoculation. After 2 weeks, when the tumors were approximately 2-3 cm in the control group with tumors (6 hamsters), all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were histologically assessed and the main organs toxicologically analyzed, including 6 control animals that had received metformin without tumor inoculation. Tumor volume was determined using the formula Lx S2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified; images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances of differences in tumor weight, volume, number of Ki-67-positive cells and other parameters were determined by the Student´s t-test.

RESULTS: Metformin inhibited fibrosarcoma growth in hamsters without toxicity. The seven-day pretreatment was important for the statistically significant effect.

CONCLUSIONS: Administration of metformin as an anti-tumor drug might be an effective and safe therapeutic approach in novel non-toxic therapies for human sarcomas.

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