Effects of triptolide on proliferation and apoptosis of acute myeloid leukemia cell line MV411 with FMS-like tyrosine kinase 3 internal tandem duplication and their mechanisms

Abstract

Objective To investigate the effects of triptolide (TP) on proliferation and apoptosis of acute myeloid leukemia cell line MV411 with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), and its effect on PI3K-Akt-mTOR pathway. Methods MTT assay was used to detect the proliferation inhibition of MV411 cell proliferation treated by different concentrations of TP in 24, 48 and 72 h. Flow cytometry was used to measure the cell apoptosis rate at 48 and 72 h. Real-time fluorescent quantitative PCR was used to detect the expression of FLT3, PTEN, PI3K, Akt, mTOR mRNA on PI3K-Akt-mTOR pathway. Results After treated by 0, 5, 10, 20, 40, and 80 nmol/L TP in 24, 48 and 72 h, the viability of MV411 cells was inhibited in a time-dose dependence manner. MV411 cells was treated by 0, 10, and 20 nmol/L TP after 48 and 72 h, the cell apoptosis rates were rising with the increasing of drug concentration, there were statistical significances [48 h:(3.30±0.20) %, (17.10±0.36) %, (35.67±0.61) %, 72 h: (7.37±0.32) %, (49.33±0.40) %, (68.92±0.11) %, all P = 0.000]. The expressions of FLT3, PI3K, Akt, and mTOR mRNA were down-regulated and PTEN mRNA expression was up-regulated by TP. Conclusion TP may inhibit the proliferation and induce apoptosis of MV411 cells by affecting the expression of PI3K-Akt-mTOR pathway related genes. Key words: Leukemia, myeloid, acute; Triptolide; Fms-like tyrosine kinase 3; Cell proliferation; Apoptosis