Screening a library of approved drugs reveals that prednisolone synergizes with pitavastatin to induce ovarian cancer cell death.

摘要: The survival rate for patients with ovarian cancer has changed little in the past three decades since introduction of platinum-based chemotherapy and new drugs are needed. Statins used treatment prevention cardiovascular diseases. Recent work from our laboratory shown that pitavastatin potential as a if dietary geranylgeraniol is controlled. However, relatively high doses statins required to induce apoptosis cells, increasing risk myopathy, most common adverse effect associated statins. This makes it desirable identify which reduce dose necessary treat cancer. A drug-repositioning strategy was employed suitable candidates. Screening custom library 100 off-patent synergistic activity identified prednisolone prominent hit. Prednisolone potentiated several assays measuring growth, or cells lines. Prednisolone, alone some cases combination pitavastatin, reduced expression genes encoding enzymes mevalonate pathway, providing mechanistic explanation synergy.