Effect of atorvastatin on tumor growth and metastasis in a breast cancer cell xenograft model and its mechanism

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 (P < 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 in vivo. These effects were not dependent on down-regulation of CYP2J2 expression.

Keywords

atorvastatin / xenograft tumor / metastasis / CYP2J2