Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Republic of Korea.
Anticancer Res. 2013 Apr;33(4):1457-62.
Chemo-resistance to cisplatin-centered cancer therapy is a major obstacle to effective disease treatment. Recently, salinomycin was proven to be highly-effective for the elimination of cancer stem cells both in vitro and in vivo. The objective of the present study was to evaluate the anticancer properties of salinomycin in cisplatin-resistant ovarian cancer cells (A2780cis).
The tetrazolium dye (MTT) assay was used to determine cell viability. Flow cytometric analysis was performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis-related proteins was evaluated by western blot analysis.
Cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. Flow cytometry showed an increase in sub-G1 phase cells. Salinomycin increased the expression of death receptor-5 (DR5), caspase-8 and Fas-associated protein with death domain (FADD). A decline in the expression of FLICE-like inhibitory protein (FLIP), activation of caspase-3 and increased poly ADP-ribose polymerase (PARP) cleavage, triggered apoptosis. Furthermore, annexin-V staining also revealed the apoptotic induction.
These findings provide important insights regarding the activation of caspase-8 and DR5, to our knowledge, for the first time in salinomycin-treated cisplatin-resistant ovarian cancer and demonstrate that salinomycin could be a prominent anticancer agent.
以顺铂为基础的癌症治疗的化疗耐药性是有效治疗疾病的主要障碍。最近，盐霉素已被证明在体外和体内对消除癌症干细胞具有高度有效性。本研究的目的是评估盐霉素在顺铂耐药卵巢癌细胞（A2780cis）中的抗癌特性。
使用四唑染料（MTT）测定法测定细胞活力。通过流式细胞术分析来分析对细胞周期和凋亡的影响。通过蛋白质印迹分析评估凋亡相关蛋白的表达。
盐霉素处理以剂量依赖性方式显著降低细胞活力。流式细胞术显示亚 G1 期细胞增加。盐霉素增加了死亡受体 5（DR5）、半胱天冬酶 8 和 Fas 相关死亡域蛋白（FADD）的表达。FLICE 样抑制蛋白（FLIP）的表达下降，激活半胱天冬酶 3 并增加多聚 ADP-核糖聚合酶（PARP）切割，引发凋亡。此外， Annexin-V 染色也显示了诱导凋亡。
这些发现为 caspase-8 和 DR5 的激活提供了重要的见解，据我们所知，这是盐霉素处理的顺铂耐药卵巢癌中的首次发现，并表明盐霉素可能是一种重要的抗癌药物。
