Low-Dose Atorvastatin has Promoting Effect on Melanoma Tumor Growth and Angiogenesis in Mouse Model

Abstract

Background: Preclinical evidence indicates that statins possess diverse antineoplastic effects in different types of tumors. However, clinical studies have yielded conflicting results regarding the potential of statins to either increase or decrease the risk of cancer. Our objective was to examine the relationship between the dose of a treatment and its impact on melanoma tumor growth and angiogenesis in an in vivo setting. Materials and Methods: Melanoma cells were injected into C57BL6 mice in four groups. They received 0, 1, 5, and 10 mg/kg of atorvastatin daily. Three others received the mentioned doses one week before the inoculation of melanoma animals. At the end of the third week, the animals were euthanized in a humane manner, and both blood samples and tumor specimens were collected for subsequent analysis. Results: The tumor size was 1.16 ± 0.25 cm3 in a group treated with therapeutic dose of atorvastatin and was significantly larger than that in the control group (0.42 ± 0.08 cm3). However, there were no significant differences between the two other doses and the control group (0.72 ± 0.22, 0.46 ± 0.08 cm3 in atorvastatin-treated groups with 5 and 10 mg/kg). The vascular density of the tumors was significantly increased in the lowest dose of the atorvastatin treatment group, similar to the results of tumor size (P < 0.05). Conclusion: Atorvastatin, at low therapeutic concentrations, has been observed to stimulate tumor growth and exhibit pro-angiogenic effects. Therefore, it is advised to exercise caution and recommend clinically relevant doses of statins to patients with cancer.

Keywords

• angiogenesis
• atorvastatin
• melanoma tumor