Caffeine induces metformin anticancer effect 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 and caffeine on fibrosarcoma in hamsters.

MATERIALS AND METHODS: 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals’ back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, 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 pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, 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 were determined by the Student’s t-test.

RESULTS: The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity.

CONCLUSIONS: Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

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