Fenbendazole (Sigma, St Louis, MO) is a benzimidazole anthelmintic which is widely used to treat helminthic infections in a number of species. It is a well-tolerated drug with few adverse effects on animal health. We tested its ability to inhibit the growth of tumors and enhance the antineoplastic effects of radiation in vivo using localized irradiation of EMT6 tumors in BALB/cRw mice. A diet containing vitamins alone or a diet supplemented with fenbendazole alone did not alter tumor growth, but the combination of both agents produced synergistic inhibition of tumor growth. The mechanism for this phenomenon warrants further study.
Tumors were induced in the abdominal flank of the mice by subcutaneous injection with 3 x 107 lymphoma cells and measured at 4-d intervals until they reached a calculated volume of 1500 mm3. The growth of unirradiated tumors treated with either diet did not differ from that of controls, but the group receiving fenbendazole plus vitamins showed a significant inhibition of tumor growth.
Cell cultures treated for 2 or 24 h with varying concentrations of fenbendazole were assayed for viability in a colony formation assay. Survival curves were plotted both as surviving fractions and yield-corrected surviving fractions, which take into account differences in cell numbers between cultures treated with and without the drug. Severe hypoxia increased the toxicity of fenbendazole to EMT6 cells, but this effect was not seen in irradiated cultures.
The fenbendazole groups initially demonstrated lower total white blood counts and neutrophil counts than the control group, but this difference was not sustained at study termination. Histopathological evaluation of the lung metastases found in all groups did not show any major differences, but the fenbendazole group had significantly less vascular invasion and necrosis of adjacent tissues than did the control group. fenben lab fenbendazol