Anti-tumor Activities of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors and Bisphosphonates in Pancreatic Cell Lines Which Show Poor Responses to Gemcitabine

Abstract

Few therapeutic options exist for gemcitabine-resistant pancreatic cancer. In this study, we investigated the anti-cancer effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors and bisphosphonates in pancreatic cancer cell lines (SUIT-2 and MIA PaCa-2) which show poor responses to gemcitabine, established through long-term culture in nutrient-deprived or gemcitabine-containing media. Under the nutrient-deprived condition, IC50s for statins and bisphosphonates decreased and those for gemcitabine increased compared with those under normal conditions. In cells cultured long-term with gemcitabine, although IC50s for gemcitabine increased, those for statins and bisphosphonates either slightly increased or remained unchanged. Thus, these drugs may be effective against pancreatic cancer cells which show poor responses to gemcitabine.