Abstract C165: Breast cancer, statins, and 3-D cell culture.

Abstract

Abstract Statins are widely used to lower serum cholesterol levels. They act by inhibiting hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in the mevalonate pathway. Recent work also shows that statins could be used as anticancer therapeutics, particularly in breast cancer. This study presents a preliminary rationale for the use of statins as a therapy in breast cancer. We characterized a panel of breast cancer cell lines for sensitivity to fluvastatin, using proliferation and cell-death assays. We also screened for differences in activity of the electron transport chain and glycolysis after fluvastatin treatment. We then began to expand on these results using 3D cell culture techniques to offer a more representative tumor model. The panel of breast cancer cell lines showed a range of sensitivity to fluvastatin, with MTT50 for 72 h treatment varying from 0.7 μM for MDA-MB231 cells to 162.8 μM in BT474 cells. Interestingly, triple negative cell lines were in the sensitive range. Differences in cell cycle populations were also observed, with a representative panel of sensitive cells showing an increased G1/G0 arrest and decrease in S-phase population when compared to insensitive cell lines. Delving deeper, mitochondrial respiration was decreased in the sensitive cell lines. We also observed greater changes in morphology in the sensitive cell lines than the insensitive when grown in 3D cell culture, potentially offering more relevance to our observations. These results confirm that there is a range of sensitivities to fluvastatin in breast cancer cell lines, allowing for further studies to determine the cause of these differences. The hints at metabolic differences could also lead to novel co-treatments with statins and greater therapeutic benefit. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C165.