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.

中文翻译：

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PRL-3抑制剂与索拉非尼联用可协同促进AML细胞凋亡。

再生肝磷酸酶 3 (PRL-3) 被认为是 AML 进展的新的独立关键驱动因素。因此，PRL-3 的特异性抑制剂将成为临床上潜在的 AML 治疗剂，但尚未有足够的临床前应用报道。在这里，我们评估了 PRL-3 抑制剂 BR-1 对 AML 细胞 ML-1 和 MOLM-13 的细胞毒性。同时，研究了BR-1对AML细胞生物学特性的影响及其机制，以及BR-1与索拉非尼联用对AML细胞活力的影响。我们的结果表明，BR-1 通过使 JAK/STAT5 和 PI3K/AKT 通路失活来促进细胞凋亡，同时通过在 S 期阻滞细胞周期来抑制细胞增殖。此外，BR-1 与索拉非尼联合使用可进一步提高对 AML 的治疗效果。因此，