The combination of PRL-3 inhibitor with sorafenib synergistically promotes AML apoptosis

Xiaomin Chen, Dade Rong, Wanhua Cai,  Xiuzhen Tong,  Haihe Wang

Abstract:

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 clinics, but there are not enough preclinical applications 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 was investigated along with the combination of BR-1 and sorafenib on the AML cell viability. Our results show that BR-1 promotes apoptosis by inactivation of the JAK/STAT5 and PI3K/AKT pathways, while inhibits cell proliferation through arresting cell cycle in the S phase. In addition, a combination of BR-1 with 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 for AML therapy.