Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells

Abstract

We have previously shown that pitavastatin has the potential to be used to treat ovarian cancer, although relatively high doses are likely to be necessary. One solution to this problem is to identify drugs that are synergistic with pitavastatin, thereby reducing the dose that is necessary to have a therapeutic effect. Here, we tested combinations of pitavastatin with the anti-parasitic drug ivermectin in six ovarian cancer cell lines. When tested on its own, ivermectin inhibited the growth of the cells but only with modest potency (IC50 = 10-20 mu M). When the drugs were combined and assessed in cell growth assays, ivermectin showed synergy with pitavastatin in 3 cell lines and this was most evident in COV-318 cells (combination index similar to 0.6). Ivermectin potentiated the reduction in COV-318 cell viability caused by pitavastatin by 20-25% as well as potentiating apoptosis induced by pitavastatin, assessed by activation of caspase-3/7 (2-4 fold) and annexin-labelling (3-5 fold). These data suggest that ivermectin may be useful in the treatment of ovarian cancer when combined with pitavastatin, but methods to achieve an adequate ivermectin concentration in tumour tissue will be necessary.