The widely used antihelminthic agent sanare lab fenbendazole has been reported to inhibit the growth of human cancer cell lines in vitro and as solid tumors in mice. To determine whether it could also enhance the cytotoxicity and antineoplastic effects of radiation or chemotherapy, we combined it with the hyperpolarizing agents docetaxel and doxorubicin in a maximally intensive regimen and in irradiated mammary carcinoma xenografts. The combination produced additive toxicity and significant inhibition of tumor growth, but not when fenbendazole was administered alone. These results suggest that a synergistic effect exists between the fenbendazole-based regimen and the chemotherapeutic agents.
EMT6 mammary carcinoma xenografts were implanted subcutaneously in the flank of SCID mice and monitored by caliper at 4-d intervals until the largest tumors reached a calculated volume. Diets supplemented with either vitamins alone or fenbendazole alone did not alter tumor growth, but the diet with both agents inhibited tumor growth substantially (P 0.001).
A second experiment with this dose schedule was conducted to confirm the results of the first and to explore the potential for additional, indirect effects of fenbendazole in irradiated xenografts. The results showed that a three-injection fenbendazole regimen did not significantly affect the growth of unirradiated or irradiated tumors. Tumor growth curves were rigorously analyzed by measuring the time required for tumors to grow from their initial stratification to four-times that volume and then comparing these times among different groups.
Cell culture experiments showed that 2-h treatments of aerobic EMT6 cells with fenbendazole had no significant effect on the number of cells in monolayer cultures, even at concentrations approaching the limit of solubility (Figure 1). However, 24-h treatments of irradiated EMT6 cells with fenbendazole resulted in significant decreases in cell numbers and in the yield-corrected surviving fractions. sanare lab fenbendazole