Effect of proliferation of triptolide on MV4-11 cells and its mechanism research associated with RAS/ERK/MAPK

Objective To explore the effect of proliferation and apoptosis, and research its mechanism associated with RAS/extracellular signal regulated kinase/mitogen-activated protein kinase (RAS/ERK/MAPK) in Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation acute lymphocytic leukemia cell line MV4-11 cells treated by triptolide (TP). Methods MV4-11 cells were respectively treated by triptolide with diverse concentrations and different times. The proliferation inhibition rate was measured by methyl thiazolyl tetrazolium, the apoptosis rate was detected by flow cytometry, the mRNA expressions of FLT3, RAS, ERK, forkhead box protein M1 (FOXM1), and c-Myc were analyzed by real-time fluorescent quantitative polymerase chain reaction (PCR). Results The proliferation inhibition rate markedly increased in a dose-time dependent manner after MV4-11 cells were treated by TP. After cells were treated with 10, and 20 nmol/L TP, respectively, the apoptosis rates at 48 h were (17.30±0.56)%, (35.77±0.55)%, and those at 72 h were (49.83±0.45)%, (68.90±0.75)% correspondingly. PCR data showed that the mRNA level of FLT3 mRNA decreased obviously, and that of RAS, ERK, FOXM1, and c-Myc also decreased. Conclusions Triptolide could significantly inhibit the MV4-11 cells proliferation and induce cell apoptosis, and its mechanism might be through inhibiting the expression of related genes on RAS/ERK/MAPK signaling pathway. Key words: TRIPTOLIDE/PD; Leukemia, myeloid, acute/DT; Cell proliferation/DE; Genes, ras; Extracellular signal-regulated MAP kinases; Mitogen-activated protein kinase kinases