洛伐他汀
药理学
医学
顺铂
阿霉素
吉西他滨
对抗
依托泊苷
他汀类
三苯氧胺
药物相互作用
甲氨蝶呤
化疗
肿瘤科
癌症
药品
内科学
乳腺癌
胆固醇
受体
作者
Kaitlyn A Khandelwal Gilman,Seungmin Han,Young‐Wook Won,Charles W. Putnam
出处
期刊:BMC Cancer
[Springer Nature]
日期:2021-04-06
卷期号:21 (1)
被引量:5
标识
DOI:10.1186/s12885-021-07963-w
摘要
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 (OD 600 ) 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.
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