Complex interactions of lovastatin with 10 chemotherapeutic drugs: a rigorous evaluation of synergism and antagonism

Abstract Background Evidence bearing on the role of statins in prevention and treatment cancer is confounded by diversity statins, chemotherapeutic agents types included numerous published studies; consequently, adjunctive value with chemotherapy remains uncertain. Methods We assayed lovastatin combination each ten commonly prescribed drugs highly reproducible vitro assays, using a neutral cellular substrate, Saccharomyces cerevisiae. Cell density (OD 600 ) data were analyzed for synergism antagonism Loewe additivity model implemented Combenefit software. Results Four – tamoxifen, doxorubicin, methotrexate rapamycin exhibited net lovastatin. The remaining six (5-fluorouracil, gemcitabine, epothilone, cisplatin, cyclophosphamide etoposide) compiled or antagonistic scores. Distinctive patterns antagonism, often coexisting within same concentration space, documented various combinations, including those Two drug pairs, combined tamoxifen also human cell lines as proof principle. Conclusions synergistic interactions because they suggest possibility clinical utility - merit further exploration validation animal models. No less importantly, strong between certain argue cautious, data-driven approach before adding statin to any regimen. urge awareness adventitious usage patients entering protocols.