Statins, besides being powerful
cholesterol-lowering drugs, also exert potent anti-proliferative activities. However, their anti-
cancer efficacy differs among the individual
statins. Thus, the aim of this study was to identify the biological pathways affected by individual
statins in an in vitro model of human
pancreatic cancer. The study was performed on a human
pancreatic cancer cell line MiaPaCa-2, exposed to all commercially available
statins (12 μM, 24 h exposure).
DNA microarray analysis was used to determine changes in the gene expression of treated cells. Intracellular concentrations of individual
statins were measured by UPLC (ultra performance liquid chromatography)-HRMS (high resolution mass spectrometer). Large differences in the gene transcription profiles of
pancreatic cancer cells exposed to various
statins were observed;
cerivastatin,
pitavastatin, and
simvastatin being the most efficient modulators of expression of genes involved namely in the
mevalonate pathway, cell cycle regulation, DNA replication, apoptosis and cytoskeleton signaling. Marked differences in the intracellular concentrations of individual
statins in
pancreatic cancer cells were found (>11 times lower concentration of
rosuvastatin compared to
lovastatin), which may contribute to inter-individual variability in their anti-
cancer effects. In conclusion, individual
statins exert different gene expression modulating effects in treated
pancreatic cancer cells. These effects may be partially caused by large differences in their bioavailability. We report large differences in gene transcription profiles of
pancreatic cancer cells exposed to various
statins. These data correlate to some extent with the intracellular concentrations of
statins, and may explain the inter-individual variability in the anti-
cancer effects of
statins.