Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells

ERK1/2 inhibitors are new promising anticancer drugs. The purpose of this research ended up being to investigate aftereffect of the mixture of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We discovered that VX-11e alone and in conjunction with voreloxin considerably decreased ERK activation in most cell lines tested. To judge the interactions from the drugs, cells were treated for twenty-four h with VX-11e or voreloxin alone as well as in combination at fixed ratios according to IC50 values. The combinatorial results of both drugs were synergistic over an array of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were discovered to be additive, one hostile and just one synergistic. The outcomes demonstrated that incubation with VX-11e and voreloxin inhibited the development of leukemia cells, affected cell cycle and caused apoptosis. In addition, the molecular mechanism of those effects may be related to an elevated expression of p21 along with a decreased expression of survivin and NF-?B in most cell lines tested except from K562 cells. To conclude, mixture of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells.