Preclinical Activity of Plitidepsin Against Clear Cell Carcinoma of the Ovary
Preclinical Activity of Plitidepsin Against Clear Cell Carcinoma of the Ovary
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DOI：
10.21873/anticanres.15232
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发表时间：
2021-09-01
影响因子：
2
通讯作者：
Mabuchi, Seiji
中科院分区：
文献类型：
--
作者：
Miyake, Ryuta;Yamanaka, Shoichiro;Mabuchi, Seiji
背景/目的：评估 Plitidepsin 对卵巢透明细胞癌 (CCC) 的抗肿瘤作用。材料和方法：通过免疫组织化学评估卵巢癌中 eEF1A2 的表达。使用卵巢 CCC 细胞系，在体外和体内评估了 Plitidepsin 的抗肿瘤作用。通过过表达或敲低 eEF1A2 的表达，我们研究了 eEF1A2 在 CCC 细胞对 Plitidepsin 敏感性中的作用。结果：76.2%的CCC中观察到eEF1A2免疫反应性，显着高于卵巢癌的其他组织学亚型。 Plitidepsin 在体外和体内均对化疗和化疗耐药的 CCC 细胞表现出显着的抗肿瘤活性。 CCC 细胞中 eEF1A2 的异位表达导致对 Plitidepsin 的敏感性增加。相反，eEF1A2 敲低降低了 CCC 细胞对 plitidepsin 的敏感性。结论：Plitidepsin 是一种靶向 eEF1A2 的新型抗癌药物，可能是治疗卵巢 CCC 的有前景的药物。
Background/Aim: To evaluate the antitumor effects of Plitidepsin against clear cell carcinoma (CCC) of the ovary. Materials and Methods: The expression of eEF1A2 in ovarian cancer was assessed by immunohistochemistry. Using ovarian CCC cell lines, the antitumor effect of Plitidepsin was assessed both in vitro and in vivo. By over-expressing or knocking down the eEF1A2 expression, we investigated the role of eEF1A2 in the sensitivity of CCC cells to Plitidepsin. Results: Immunoreactivity to eEF1A2 was observed in 76.2% of CCC, which was significantly higher than other histological subtypes of ovarian cancer. Plitidepsin exhibited significant antitumor activity toward chemonaive and chemoresistant CCC cells both in vitro and in vivo. Ectopic expression of eEF1A2 in CCC cells resulted in increased sensitivity to Plitidepsin. In contrast, eEF1A2 knockdown decreased sensitivity of CCC cells to plitidepsin. Conclusion: Plitidepsin, a novel anti-cancer agent that targets eEF1A2, may be a promising agent for treating ovarian CCC.