Jawad Mohammed Jasim, Richardson Alan
The School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Stoke-on-Trent ST4 7QB, Staffordshire, UK.
College of Veterinary Medicine, Kerbala University, Karbala 56001, Iraq.
Diseases. 2023 Mar 14;11(1):49. doi: 10.3390/diseases11010049.
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 (IC = 10-20 µM). 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 ~ 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.
我们之前已经表明，匹伐他汀有潜力用于治疗卵巢癌，尽管可能需要相对高的剂量。解决这个问题的一个办法是鉴定与匹伐他汀具有协同作用的药物，从而降低产生治疗效果所需的剂量。在此，我们在六种卵巢癌细胞系中测试了匹伐他汀与抗寄生虫药物伊维菌素的组合。单独测试时，伊维菌素能抑制细胞生长，但效力适中（IC = 10 - 20 µM）。当将这两种药物组合并在细胞生长试验中进行评估时，伊维菌素在3种细胞系中与匹伐他汀表现出协同作用，这在COV - 318细胞中最为明显（联合指数约为0.6）。伊维菌素使匹伐他汀引起的COV - 318细胞活力降低增强了20 - 25%，同时也增强了匹伐他汀诱导的细胞凋亡，通过半胱天冬酶 - 3/7的激活（2 - 4倍）和膜联蛋白标记（3 - 5倍）来评估。这些数据表明，伊维菌素与匹伐他汀联合使用时可能对卵巢癌治疗有用，但需要找到在肿瘤组织中达到足够伊维菌素浓度的方法。
