Frontiers of Medicine
>> 2009,
Volume 3,
Issue 4
doi:
10.1007/s11684-009-0079-5
Effect of atorvastatin on tumor growth and metastasis
in a breast cancer cell xenograft model and its mechanism
1.Department of Nephrology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, Wuhan 430030, China; 2.Department of Cardiology,
Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, Wuhan 430030, China;
Available online: 2009-12-05
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Abstract
This paper aims to evaluate the effects and the possible mechanisms of atorvastatin on tumor growth and metastasis in a xenograft tumor model. Twenty-four female athymic BALB/C mice with MDA-MB-435 xenograft tumors were randomly assigned to three groups: a control group, a low-dose atorvastatin treatment group, and a high-dose atorvastatin treatment group. The mice in the treatment groups began to be administered with atorvastatin (10 or 20 mg/kg per day) when the xenograft tumors reached 1 cm in diameter. At the end of the experiment, the tumor volume and weight and the lung metastasis colonies of each mouse were measured. Western blotting was applied to detect phosphorylation of protein kinase B (PKB, Akt), extracellular signal regulated kinase (ERK), c-Jun N-terminal Kinase (JNK), and the expression of cytochrome P450 (CYP) subtype CYP2J2. Atorvastatin suppressed xenograft tumor growth and metastasis both in the low-dose and the high-dose treatment groups ( < 0.05). Atorvastatin also decreased the phosphorylated Akt (p-Akt) and p-ERK but increased p-JNK expression. However, atorvastatin did not alter the expression of CYP2J2 in tumor tissue. This suggests that atorvastatin has the efficacy of suppressing tumor growth and metastasis . These effects were not dependent on down-regulation of CYP2J2 expression.
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