Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane.
Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane.
复制标题
DOI：
10.1155/2013/872957
复制
发表时间：
2013
影响因子：
--
通讯作者：
Tollefsbol TO
中科院分区：
文献类型：
--
作者：
Chen H;Landen CN;Li Y;Alvarez RD;Tollefsbol TO
由于对常规化疗产生耐药性，晚期卵巢癌的特点是死亡率高。能够提高卵巢癌常规化疗疗效的新型化合物可能会克服这种耐药性。食用绿茶(表没食子儿茶素没食子酸酯，EGCG)和十字花科蔬菜(萝卜硫素，SFN)与卵巢癌的发生呈负相关，并通过靶向癌细胞中的多个分子起到抗癌作用。然而，EGCG和SFN联合治疗对卵巢癌细胞的影响以及顺铂对这些细胞的疗效尚不清楚。在这项研究中，EGCG或SFN被用来单独或联合顺铂治疗顺铂敏感(A2780)和顺铂耐药(A2780/CP20)的卵巢癌细胞。我们发现，EGCG和SFN联合作用可降低两种卵巢癌细胞系的细胞活力，且呈时间和剂量依赖性。此外，EGCG和SFN联合应用可增强顺铂诱导的细胞凋亡和G2/M期阻滞，从而增强顺铂对顺铂敏感和耐药卵巢癌细胞的疗效。EGCG和SFN联合治疗可上调顺铂诱导的顺铂敏感卵巢癌细胞中p21的表达，而p27的表达不受这两种处理的影响。总的来说，这些研究提供了克服卵巢癌顺铂化疗耐药性的新方法。
Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG) and cruciferous vegetables (sulforaphane, SFN) is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780/CP20) ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.