PDF(Pubmed)
Abstract：
Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen \"green\" natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
摘要：
谷胱甘肽S-转移酶（GST）的过表达可促进肝细胞癌（HCC）治疗中顺铂的耐药。因此，抑制GST是提高HCC治疗中顺铂敏感性的有吸引力的策略。尽管已经开发了几种合成的GST抑制剂，抗癌的副作用和窄谱严重限制了其临床应用。考虑到具有抗癌活性的天然化合物的丰度，这项研究开发了一种快速荧光技术来筛选具有高特异性的“绿色”天然GST抑制剂。荧光分析表明，从血童分离的五酸内酯B（以下简称C1）在体外和体内显着下调了顺铂耐药HCC细胞中的GST水平。重要的是,C1可以从正常肝细胞中选择性杀死HCC细胞，通过下调GST表达,有效提高顺铂对肝癌小鼠的治疗效果。考虑到肝癌患者的高GST水平，该化合物在临床实践中通过下调GST水平显示出对HCC治疗增敏的高潜力.
