[Combination of Homoharringtonine with Arsenic Trioxide Induces Apoptosis of Human Acute Myeloid Leukemia Cell Line U937]

Abstract

Objective: To investigate the effects and mechanisms of the combination of homoharringtonine (HHT) with arsenic trioxide(As₂O₃) on human myeloid cell line U937 in vitro.

Methods: MTT method was used to determine the antiproliferating effect of different concentrations of HHT, As₂O₃ and their combination on U937 cells; the flow cytometry with Annexin-V-FITC/PI double staining was used to determine the apoptosis-induced effect of HHT and As₂O₃ alone or their combination; Western blot method was used to detect the protein expression of P-Akt^Ser473,P-Akt^Thr308,BCL-XL, BID,MCL-1,P-MCL-1 and so on.

Results: HHT and As₂O₃ could significantly inhibit proliferation of U937 cells and induce their apoptosis. The combination of these 2 drugs could significantly enhance the early apoptosis of U937 cells. After combination of these 2 drugs was used, the protein expressions of P-Akt^Ser473,P-Akt^Thr308,MCL-1,P-MCL-1 and BCL-XL were obviously down-regulated, but the expression of BID protein did not change.

Conclusion: The combination treatment of HHT and As₂O₃ can synergistically inhibit the growth of U937 cells through inhibition of PI3K/Akt signal way and MCL-1 protein.