Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Pharmacogenomics. 2013 Aug;14(11):1305-17. doi: 10.2217/pgs.13.122.
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.
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.
TPL is able to enhance drug sensitivity of resistant myeloid leukemia cell lines through downregulation of HIF-1α and Nrf2.
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。
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。
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。
TPL 通过下调 HIF-1α 和 Nrf2 增强耐药髓系白血病细胞系对药物的敏感性。
