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- Title
Chemically induced mouse liver tumors are resistant to treatment with atorvastatin.
- Authors
Braeuning, Albert; Bucher, Philip; Hofmann, Ute; Buchmann, Albrecht; Schwarz, Michael
- Abstract
Background: Atorvastatin is a potent inhibitor of the mevalonate pathway and widely used as a hypolipidemic drug. Some epidemiological studies and animal experiments indicate that the long-term use of atorvastatin and structurally related drugs might be associated with a reduced risk of developing hepatocellular carcinoma (HCC), the most common hepatocellular malignancy in humans. However, the potential of atorvastatin to inhibit HCC formation is controversially discussed. Methods: Hepatocellular tumors were chemically induced by treatment of C3H/He mice with 10 µg/g body weight N-nitrosodiethylamine and the ability of atorvastatin to interfere with tumor formation was investigated by treatment of mice with 0.1% atorvastatin in the diet for 6 months. Tumor size and tumor multiplicity were analyzed, as were tissue levels of cholesterol and atorvastatin. Results: Atorvastatin treatment efficiently reduced serum cholesterol levels. However, the growth of tumors driven by activated MAPK (mitogen-activated protein kinase) signaling was not attenuated by the presence of the drug, as evidenced by a lack of reduction of tumor volume or tumor multiplicity by atorvastatin. Levels of the atorvastatin uptake transporters Oatp1a4 and Oatp1b2 were down-regulated at the mRNA and protein levels in chemically induced mouse liver tumors, but without striking effects on atorvastatin concentrations in the tumor tissue. Conclusion: In summary, the present data provide substantial evidence that atorvastatin does not beneficially influence tumor growth in mouse liver and thereby challenge the hypothesis that statin use might protect against hepatocellular cancer.
- Subjects
TUMOR treatment; LIVER tumors; ATORVASTATIN; MEVALONATE kinase; N-Nitrosodiethylamine; DRUG resistance in cancer cells
- Publication
BMC Cancer, 2014, Vol 14, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-14-766