Feili Chen

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

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.

Idarubicin is superior to daunorubicin in remission induction of de novo acute myeloid leukemia patients with high MDR1 expression.

AIM To investigate whether idarubicin in a cytarabine-based induction regimen was superior to daunorubicin in de novo acute myeloid leukemia patients expressing high MDR1. PATIENTS & METHODS The clinicopathological data were analyzed in 125 patients receiving daunorubicin or idarubicin with cytarabine for remission induction. Median MDR1 mRNA expression in pretreated bone marrow cells was used as the cutoff point for high and low MDR1 expression. RESULTS A total of 59.7% high and 77.8% low MDR1 expressers achieved complete remission (CR; p = 0.029). Idarubicin yielded a higher CR rate than daunorubicin in high MDR1 expressers (82.1 vs 41.2%; p = 0.001), it also demonstrated a higher CR rate than daunorubicin (p < 0.05) in high MDR1 expressers exhibiting favorable or intermediate risk, while there was no difference between the two treatment arms in low MDR1 expressers exhibiting either favorable or intermediate risk. CONCLUSION Idarubicin is associated with better remission induction of de novo acute myeloid leukemia patients with high MDR1 expression.