Comparative Study of Lipophilic Statin Activity in 2D and 3D in vitro Models of Human Breast Cancer Cell Lines MDA-MB-231 and MCF-7

Abstract

Introduction: Statins are a type of drugs that are used to lower cholesterol level in blood. Since the early 1990s, it has been known that statins could be beneficial in cancer therapy. However, data remain controversial, especially regarding estrogen receptors status. Despite many studies in breast cancer models in vitro, the correlations of effects of separate statins in various model systems remain unclear.

Aim: Our aim was to evaluate the anticancer activity of lovastatin, mevastatin, pitavastatin and simvastatin on different subtypes of human breast cancer (MDA-MB-231 and MCF-7 cell lines) in spatially different 2D and 3D cultures in vitro.

Materials and methods: Cell viability was tested using MTT assay. Effect of statins on cell colony formation was evaluated by calculating breast cancer cell colony area and number. The effect on cell migration was estimated by "wound healing" assay. The activity of compounds in 3D cultures was evaluated by measuring the spheroid size changes during incubation.

Results: Among the tested statins, pitavastatin had the greatest effect on the viability of breast cancer MDA-MB-231 and MCF-7 cell lines. The mevastatin and pitavastatin mostly decreased the MDA-MB-231 and MCF-7 cell colony formation. All statins at 90% of their estimated effective concentration (EC₅₀) and simvastatin at 10% of its EC₅₀ concentration suppressed the MCF-7 cells migration in "wound healing" assay. Only higher concentrations of mevastatin and pitavastatin slowed down the MDA-MB-231 cell migration. Statins showed different activity on 3D cell cultures growth. Lovastatin and simvastatin delayed the growth of MDA-MB-231 cell spheroids, while mevastatin and pitavastatin reduced the growth of MCF-7 spheroids.

Conclusion: Statins possess different anticancer activity in human breast cancer MDA-MB-231 and MCF-7 cell cultures. Pitavastatin and simvastatin showed the highest activity in most tested assays, especially against MCF-7 cell line.

Keywords: breast cancer; cell colonies; cell migration; cell viability; statins; tumor spheroid.