Atorvastatin enhances the antitumor activity of tamoxifen in B16f10 mouse melanoma cell lines

Abstract

Introduction: Tamoxifen has been used in the treatment of metastatic malignant melanoma more common with other agents in the combined therapy. Up-regulated activity of the mevalonate pathway has been shown in a range of different cancers. Atorvastatin is the most commonly used statin approved for cholesterol reduction by inhibiting the mevalonate pathway and has been shown to inhibit tumor growth. In the present study, we used atorvastatin and tamoxifen combination therapy on B16f10 mouse melanoma cell lines to study whether atorvastatin could increase the sensitivity of melanoma cells to the chemotherapeutic agent such as tamoxifen. Methods: The cell line was treated with different concentrations of tamoxifen and/or atorvastatin for 24 and 48h and the effects of treatment on p53 and RhoA were investigated using quantitative RT-PCR. Results: The combination of atorvastatin and tamoxifen resulted in a potentiation antitumor effect via up-regulation of p53 and down-regulation of RhoA expression against melanoma tumors in vitro. Furthermore, we demonstrated the combination of atorvastatin with tamoxifen could reduce tamoxifen dose to minimize possible detrimental side effects in melanoma. Conclusion: Our results suggested that atorvastatin as a combined therapy with tamoxifen may provide a new approach for improving the efficacy and treating against melanoma cancer but needs further exploration in clinical trials.