Wang Chia-Woei, Lee Bao-Hong, Tai Chen-Jei
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan.
Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan.
Oncotarget. 2017 Dec 5;8(67):111912-111921. doi: 10.18632/oncotarget.22951. eCollection 2017 Dec 19.
Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 μM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells. Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while TGF-beta treatment significantly increased the expression of vimentin and PGC-1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the action of Cd on cancer stemness may contribute to the regulation of epithelial-mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.
化疗是卵巢癌的主要治疗方法之一。癌症干细胞(CSCs)会逃避化疗并导致化疗耐药。我们之前证明了虫草素(Cd)可抑制人卵巢癌细胞的转移,本研究的目的是探究Cd对卵巢癌干性的影响。使用转化生长因子-β(TGF-β)诱导SKOV-3卵巢癌细胞对化疗药物顺铂产生耐药性。用100μM的Cd处理后,TGF-β诱导的SKOV-3细胞的细胞活力、癌症干细胞百分比和基质金属蛋白酶(MMPs)水平均降低。Cd处理可恢复E-钙黏蛋白水平并抑制波形蛋白水平,而TGF-β处理则显著增加SKOV-3细胞中波形蛋白和PGC-1α 的表达,并降低E-钙黏蛋白水平,这表明Cd对癌症干性的作用可能有助于调节上皮-间质转化(EMT)。Cd有效减弱了TGF-β在SKOV-3癌症干细胞中引起的化疗耐药性,以增强顺铂的细胞毒性。