Combination of PRL-3 Inhibitor with Sorafenib Synergistically Promotes AML Apoptosis

Phosphatase of regenerating liver-3 (PRL-3) is recognized as a novel independent crucial driver for AML progression. Thus, the specific inhibitor of PRL-3 would be a potential therapeutic agent to AML in clinic, but there is no such preclinical application reported yet. Here we evaluated the cytotoxicity of PRL-3 inhibitor, BR-1, against AML cells ML-1 and MOLM-13. Meanwhile, the effect of BR-1 on the biological characteristics of AML cells and the underlying mechanism were investigated along with the combination of BR-1 and sorafenib on AML cell viability. Our results show that BR-1 promotes apoptosis by inactivation of JAK/STAT5 and PI3K/AKT pathways, while inhibits cell proliferation through arresting cell cycle in the S phase. In addition, combination of BR-1 with a FLT3 inhibitor, sorafenib can further improve the therapeutic effect on AML. Thus, our results demonstrated that BR-1 would be a novel and potent therapeutic agent to AML, and its combination with other anti-AML drugs would be a promising strategy to AML therapy.