Polyether ionophore salinomycin (SAL) and its semi-synthetic derivatives are recognized as very promising anticancer drug candidates due to their activity against various types of cancer cells, including multidrug-resistant populations. Ovarian cancer is the deadliest among gynecologic malignancies, which is connected with the development of chemoresistant forms of the disease in over 70% of patients after initial treatment regimen. Thus, we decided to examine the anticancer properties of SAL and selected SAL derivatives against a series of drug-sensitive (A2780, SK-OV-3) and derived drug-resistant (A2780 CDDP, SK-OV-3 CDDP) ovarian cancer cell lines. Although SAL analogs showed less promising IC50 values than SAL, they were identified as the antitumor agents that significantly overcome the resistance to platinum-based drugs in ovarian cancer, more potent than unmodified SAL and commonly used anticancer drugs—5-fluorouracil, gemcitabine, and cisplatin. Moreover, when compared with SAL used alone, our experiments proved for the first time increased selectivity of SAL-based dual therapy with 5-fluorouracil or gemcitabine, especially towards A2780 cell line. Looking closer at the results, SAL acted synergistically with 5-fluorouracil towards the drug-resistant A2780 cell line. Our results suggest that combinations of SAL with other antineoplastics may become a new therapeutic option for patients with ovarian cancer.

中文翻译：

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用盐霉素及其衍生物克服卵巢癌对铂类药物的耐药性——一项体外研究

聚醚离子载体盐霉素 (SAL) 及其半合成衍生物被认为是非常有前景的抗癌药物候选物，因为它们对各种类型的癌细胞（包括多药耐药群体）具有活性。卵巢癌是妇科恶性肿瘤中最致命的，这与初始治疗方案后超过 70% 的患者出现该疾病的化学抗性形式有关。因此，我们决定检查 SAL 和选定的 SAL 衍生物对一系列药物敏感（A2780、SK-OV-3）和衍生的耐药（A2780 CDDP、SK-OV-3 CDDP）卵巢癌细胞的抗癌特性线。尽管 SAL 类似物的 IC50 值不如 SAL，但它们被确定为抗肿瘤剂，可显着克服卵巢癌对铂类药物的耐药性，比未修饰的 SAL 和常用的抗癌药物——5-氟尿嘧啶、吉西他滨和顺铂更有效。此外，与单独使用 SAL 相比，我们的实验首次证明了使用 5-氟尿嘧啶或吉西他滨的基于 SAL 的双重治疗的选择性增加，尤其是对 A2780 细胞系。仔细观察结果，SAL 与 5-氟尿嘧啶协同作用于耐药 A2780 细胞系。我们的结果表明，SAL 与其他抗肿瘤药物的组合可能成为卵巢癌患者的新治疗选择。特别是对 A2780 细胞系。仔细观察结果，SAL 与 5-氟尿嘧啶协同作用于耐药 A2780 细胞系。我们的结果表明，SAL 与其他抗肿瘤药物的组合可能成为卵巢癌患者的新治疗选择。特别是对 A2780 细胞系。仔细观察结果，SAL 与 5-氟尿嘧啶协同作用于耐药 A2780 细胞系。我们的结果表明，SAL 与其他抗肿瘤药物的组合可能成为卵巢癌患者的新治疗选择。