雷公藤红素，一种中药提取物，通过下调 HIF-1α 和 Nrf2 增强耐药髓系白血病细胞系的药物敏感性。

Triptolide, a Chinese herbal extract, enhances drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.

出版信息

Pharmacogenomics. 2013 Aug;14(11):1305-17. doi: 10.2217/pgs.13.122.

DOI:10.2217/pgs.13.122

PMID:23930677

Abstract

AIM

To explore whether triptolide (TPL) can enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.

MATERIALS & METHODS: HL60/A and K562/G cells were subjected to different treatments and thereafter an methyl thiazole tetrazolium bromide assay, flow cytometry, western blot and real-time PCR were used to determine IC₅₀, apoptotic status and expression of Nrf2, HIF-1α and their target genes.

RESULTS

Doxorubicin- or imatinib-induced apoptosis was enhanced when anticancer agents were used in combination with TPL. When combined with TPL, both doxorubicin and imatinib downregulate Nrf2 and HIF-1α expression at protein and mRNA levels. Genes downstream of Nrf2, for example, NQO1, GSR and HO-1, as well as target genes of HIF-1α, for example, BNIP3, VEGF and CAIX are also downregulated at the mRNA level.

CONCLUSION

TPL is able to enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.

摘要

目的

探讨雷公藤红素（TPL）是否通过下调 HIF-1α 和 Nrf2 来增强耐药髓系白血病细胞系对药物的敏感性。

材料与方法

HL60/A 和 K562/G 细胞分别接受不同处理，然后采用噻唑蓝溴化法（MTT 法）、流式细胞术、Western blot 和实时 PCR 检测细胞 IC₅₀、细胞凋亡情况以及 Nrf2、HIF-1α 及其靶基因的表达。

结果

当与 TPL 联合使用时，阿霉素或伊马替尼诱导的细胞凋亡增加。与 TPL 联合使用时，阿霉素和伊马替尼均下调 Nrf2 和 HIF-1α 蛋白和 mRNA 水平的表达。Nrf2 的下游基因，如 NQO1、GSR 和 HO-1，以及 HIF-1α 的靶基因，如 BNIP3、VEGF 和 CAIX，在 mRNA 水平也下调。