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Updated: Aug 2, 2026
A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
Chemically induced mouse liver tumors are resistant to treatment with atorvastatin
Albert Braeuning1, Philip Bucher, Ute Hofmann
1Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tuebingen, Wilhelmstr, 56, Tuebingen 72074, Germany. albert.braeuning@uni-tuebingen.de.
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.
Insights
Atorvastatin, a cholesterol-lowering drug, did not inhibit liver tumor growth in mice. This study challenges the idea that statin use may protect against hepatocellular carcinoma (HCC).
Area of Science:
- Hepatology
- Oncology
- Pharmacology
Background:
- Atorvastatin is a widely used hypolipidemic drug that inhibits the mevalonate pathway.
- Epidemiological and animal studies suggest statins may reduce hepatocellular carcinoma (HCC) risk, but this is debated.
- The potential of atorvastatin to inhibit HCC formation requires further investigation.
Purpose of the Study:
- To investigate the effect of atorvastatin on chemically induced liver tumor formation in mice.
- To determine if atorvastatin influences tumor size and multiplicity.
- To assess the impact of atorvastatin on cholesterol and drug levels in tumor tissue.
Main Methods:
- Hepatocellular tumors were induced in C3H/He mice using N-nitrosodiethylamine.
- Mice were treated with 0.1% atorvastatin in their diet for 6 months.
- Tumor size, multiplicity, and tissue levels of cholesterol and atorvastatin were analyzed.
Main Results:
- Atorvastatin significantly reduced serum cholesterol levels.
- Tumor volume and multiplicity were not reduced by atorvastatin treatment, even in tumors with activated MAPK signaling.
- Atorvastatin uptake transporters (Oatp1a4, Oatp1b2) were downregulated in tumors, but atorvastatin concentrations in tumor tissue were not significantly affected.
Conclusions:
- Atorvastatin does not beneficially affect tumor growth in a mouse model of liver cancer.
- These findings challenge the hypothesis that statin use offers protection against hepatocellular cancer.
- Further research is needed to clarify the role of statins in cancer prevention.
