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BMC Cancer
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Statins | Research article

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

Authors: Kaitlyn A. Khandelwal Gilman, Seungmin Han, Young-Wook Won, Charles W. Putnam

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

Evidence bearing on the role of statins in the prevention and treatment of cancer is confounded by the diversity of statins, chemotherapeutic agents and cancer types included in the numerous published studies; consequently, the adjunctive value of statins with chemotherapy remains uncertain.

Methods

We assayed lovastatin in combination with each of ten commonly prescribed chemotherapy drugs in highly reproducible in vitro assays, using a neutral cellular substrate, Saccharomyces cerevisiae. Cell density (OD600) data were analyzed for synergism and antagonism using the Loewe additivity model implemented with the Combenefit software.

Results

Four of the ten chemotherapy drugs – tamoxifen, doxorubicin, methotrexate and rapamycin – exhibited net synergism with lovastatin. The remaining six agents (5-fluorouracil, gemcitabine, epothilone, cisplatin, cyclophosphamide and etoposide) compiled neutral or antagonistic scores. Distinctive patterns of synergism and antagonism, often coexisting within the same concentration space, were documented with the various combinations, including those with net synergism scores. Two drug pairs, lovastatin combined with tamoxifen or cisplatin, were also assayed in human cell lines as proof of principle.

Conclusions

The synergistic interactions of tamoxifen, doxorubicin, methotrexate and rapamycin with lovastatin – because they suggest the possibility of clinical utility - merit further exploration and validation in cell lines and animal models. No less importantly, strong antagonistic interactions between certain agents and lovastatin argue for a cautious, data-driven approach before adding a statin to any chemotherapeutic regimen. We also urge awareness of adventitious statin usage by patients entering cancer treatment protocols.
Appendix
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Footnotes
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Metadata
Title
Complex interactions of lovastatin with 10 chemotherapeutic drugs: a rigorous evaluation of synergism and antagonism
Authors
Kaitlyn A. Khandelwal Gilman
Seungmin Han
Young-Wook Won
Charles W. Putnam
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07963-w

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