Effects of metformin and its combinations with other repurposed drugs on fibrosarcoma in hamsters

Abstract

Introduction/Objective. Many drugs registered for various other indications can act selectively on tumor receptors, signaling pathways, metabolic processes, bioenergetic factors, enzymes, proteins and genes that regulate tumor proliferation, apoptosis and neoangiogenesis without affecting these activities in healthy cells. Introduction of new drugs is a very long, complex and expensive process of research. Detecting an anticancer effect in drugs already registered for other indications and forming their combinations may directly reduce the time and cost of such research. Methods. Anticancer efficacy of metformin and its combinations with caffeine, itraconazole and nitroglycerin was tested on fibrosarcoma experimentally induced by BHK21/C13 cells in Syrian golden hamsters (six animals per group, randomly allocated to control and experimental groups, doses equivalent to usual human doses). After animal sacrifice, tumors were excised and their size, biophysical characteristics, histology and immunohistochemistry were assessed. Blood samples were collected for hematological and biochemical analyses and the main organs were toxicologically analyzed. Statistical significance was determined by one-way ANOVA followed by the Student-Newman-Keuls post hoc test. Results. Two-drug combinations of metformin with caffeine or itraconazole or nitroglycerin showed significant antitumor effects on hamster fibrosarcoma compared to control, regarding all tested tumor parameters (p < 0.05) without toxicity. Conclusion. Administration of metformin in combination with caffeine or itraconazole or nitroglycerin might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.