The Influence of Statin Use on Chemotherapeutic Efficacy in Studies of Mouse Models: A Systematic Review

Overview

Journal Anticancer Res

Specialty Oncology

Date 2023 Sep 29

PMID 37772570

Authors

Angela Tulk

Raj Watson

Jennifer Erdrich

Affiliations

Soon will be listed here.

Abstract

Background/aim: Using statins as antitumor agents is an approach to cancer therapy that has been explored extensively in specific cancer types. Reframing the query to how a statin interacts with the treatment regimen instead might provide new insight. Given that cell-cycle regulation influences tumorigenesis, it is possible that the cell-cycle phase which a given chemotherapy acts on influences the synergistic effects with adjuvant statin use. In this review, we outline the effect of statins in combination with chemotherapeutic drugs in in vivo animal model studies based on the class of chemotherapy and its relation to the cell cycle.

Materials And Methods: This systematic review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 with 23 articles deemed eligible to be included.

Results: Our review suggests that statins influence the success of chemotherapy treatments. Furthermore, enhanced efficacy was demonstrated with chemotherapeutic drugs that act at every phase of the cell cycle.

Conclusion: This type of compilation departs from the norm of describing statin influence on named cancer subtypes and instead catalogs how statins interact with categorical chemotherapy agents which might be beneficial for broader therapeutic decision-making across cancer subtypes, possibly contributing to pharmaceutical development, and thereby helping to maximize patient outcomes.

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References

Zhao Y, Wu T, Zhao M, Li C . The balance of protein farnesylation and geranylgeranylation during the progression of nonalcoholic fatty liver disease. J Biol Chem. 2020; 295(15):5152-5162. PMC: 7152775. DOI: 10.1074/jbc.REV119.008897. View

Brown M, Faust J, Goldstein J, Kaneko I, Endo A . Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. J Biol Chem. 1978; 253(4):1121-8. View

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015; 4:1. PMC: 4320440. DOI: 10.1186/2046-4053-4-1. View

Pereira P, Sharma S, Carter L, Edwards K, Pourat J, Ragupathi A . Caveolin-1 mediates cellular distribution of HER2 and affects trastuzumab binding and therapeutic efficacy. Nat Commun. 2018; 9(1):5137. PMC: 6277446. DOI: 10.1038/s41467-018-07608-w. View

Sun Y, Liu Y, Ma X, Hu H . The Influence of Cell Cycle Regulation on Chemotherapy. Int J Mol Sci. 2021; 22(13). PMC: 8267727. DOI: 10.3390/ijms22136923. View

Ding N, Cui X, Gao Z, Huang H, Wei X, Du Z . A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors. Int J Oncol. 2014; 44(6):2139-45. PMC: 4063540. DOI: 10.3892/ijo.2014.2350. View

Bilheimer D, Grundy S, Brown M, Goldstein J . Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci U S A. 1983; 80(13):4124-8. PMC: 394213. DOI: 10.1073/pnas.80.13.4124. View

Mangelinck A, Habel N, Mohr A, Gaspar N, Stefanovska B, Fromigue O . Synergistic Anti-Tumor Effect of Simvastatin Combined to Chemotherapy in Osteosarcoma. Cancers (Basel). 2021; 13(22). PMC: 8616540. DOI: 10.3390/cancers13225869. View

Chen J, Lan T, Hou J, Zhang J, An Y, Tie L . Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1. Int J Biochem Cell Biol. 2012; 44(5):759-69. DOI: 10.1016/j.biocel.2012.01.015. View

10.

Kovanen P, Bilheimer D, Goldstein J, Jaramillo J, Brown M . Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci U S A. 1981; 78(2):1194-8. PMC: 319974. DOI: 10.1073/pnas.78.2.1194. View

11.

Jiang P, Mukthavaram R, Mukthavavam R, Chao Y, Bharati I, Fogal V . Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs. J Transl Med. 2014; 12:13. PMC: 3898565. DOI: 10.1186/1479-5876-12-13. View

12.

Sadok A, Marshall C . Rho GTPases: masters of cell migration. Small GTPases. 2014; 5:e29710. PMC: 4107589. DOI: 10.4161/sgtp.29710. View

13.

Ciocca D, Rozados V, Cuello Carrion F, Gervasoni S, Matar P, Scharovsky O . Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin. Cell Stress Chaperones. 2003; 8(1):26-36. PMC: 514851. DOI: 10.1379/1466-1268(2003)8<26:hahirt>2.0.co;2. View

14.

Pan Q, Xu J, Ma L . Simvastatin enhances chemotherapy in cervical cancer via inhibition of multiple prenylation-dependent GTPases-regulated pathways. Fundam Clin Pharmacol. 2019; 34(1):32-40. DOI: 10.1111/fcp.12479. View

15.

Xu B, Muramatsu T, Inazawa J . Suppression of MET Signaling Mediated by Pitavastatin and Capmatinib Inhibits Oral and Esophageal Cancer Cell Growth. Mol Cancer Res. 2021; 19(4):585-597. DOI: 10.1158/1541-7786.MCR-20-0688. View

16.

Feleszko W, Mlynarczuk I, Olszewska D, Jalili A, Grzela T, Lasek W . Lovastatin potentiates antitumor activity of doxorubicin in murine melanoma via an apoptosis-dependent mechanism. Int J Cancer. 2002; 100(1):111-8. DOI: 10.1002/ijc.10440. View

17.

Endo A, Kuroda M, Tsujita Y . ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot (Tokyo). 1976; 29(12):1346-8. DOI: 10.7164/antibiotics.29.1346. View

18.

Feng J, Dai W, Mao Y, Wu L, Li J, Chen K . Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis. J Exp Clin Cancer Res. 2020; 39(1):24. PMC: 6993409. DOI: 10.1186/s13046-020-1528-x. View

19.

Moon D, Lee H, Lee Y, Chung M, Park J, Park S . Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer. Yonsei Med J. 2016; 57(5):1124-30. PMC: 4960377. DOI: 10.3349/ymj.2016.57.5.1124. View

20.

Kou X, Jiang X, Liu H, Wang X, Sun F, Han J . Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer. Cancer Sci. 2018; 109(10):3272-3284. PMC: 6172049. DOI: 10.1111/cas.13748. View