摘要
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 downregulating 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.
基金
supported by the National Natural Science Foundation of China(Grant Nos.:82003931,82204766 and 81374062)
the Outstanding Youth Foundation of Hunan Provincial Education Department of China(Grant No.:20B445)
the Hunan Youth Science and Technology Innovation Talents Project,China(Grant No.:2021RC3100)
the Chinese Postdoctoral Science foundation(Grant No.:2021M690974)
Changjiang Scholars Program in Ministry Education,People's Republic of China(Program No.:T2019133)
the Scientific Research Project of Hunan Provincial Education Department(Project No.:21B0394).
