Combination of ERK2 and STAT3 Inhibitors Promotes Anticancer Effects on Acute Lymphoblastic Leukemia Cells

Background/aim: Deregulated activation of signaling with the RAS/RAF/mitogen-activated protein kinase/extracellular signal-controlled kinase (RAS/RAF/MEK/ERK) and signal transducer and activator of transcription (STAT) pathways is involved with numerous hematological malignancies, which makes it a beautiful therapeutic target. This research aimed to evaluate the result from the mixture of ERK2 inhibitor VX-11e and STAT3 inhibitor STA-21 on acute lymphoblastic leukemia cell lines REH and MOLT-4.

Materials and techniques: REH and MOLT-4 cell lines were cultured with every drug alone as well as in combination. Cell viability, ERK activity, cell cycle distribution, apoptosis and oxidative stress induction were assessed by flow cytometry. Protein amounts of STAT3, phospho-STAT3, protein tyrosine phosphatase 4A3 (PTP4A3), survivin, p53 and p21 were based on western blotting.

Results: VX-11e in conjunction with STA-21 considerably inhibited cell viability, caused G0/G1 cell-cycle arrest, enhanced manufacture of reactive oxygen species, and caused apoptosis. These effects were connected by having an elevated degree of p21 protein in REH cells with reduced amounts of phopho-STAT3, survivin and PTP4A3 proteins in MOLT-4 cells.

Conclusion: Our findings give a rationale for combined inhibition of RAS/RAF/MEK/ERK and STAT3 pathways so they can improve anticancer effects against acute lymphoblastic VX-11e leukemia cells.