Chrysophanol suppresses growth and metastasis of T cell acute lymphoblastic leukemia via miR-9/PD-L1 axis

Abstract

T cell acute lymphoblastic leukemia (T-ALL) was a malignant lymphoma. Therefore, the development of novel therapeutic agents against T-ALL is imperative. Previous studies have shown that chrysophanol (CHL), an anthraquinone compound isolated from the Rheum palmatum L., exerts anti-proliferative and anti-metastatic effects in multiple malignant tumors. However, the effect of CHL on the progression of TALL is poorly understood. The aim of this study was to explore the role of CHL in the biological behavior of T-ALL cells and determine its underlying mechanism. Both T-ALL cell lines (Jurkat and TALL-104) were treated with CHL. The proliferation, apoptosis, migration, and invasion of T-ALL cells were determined by CCK-8, flow cytometry, wound healing, and Transwell assay, respectively. Western blot and RT-qPCR were applied to examine gene expression. The dual-luciferase reporter gene assay was employed to examine the regulation mechanism of miR-9 and PD-L1. A T-ALL xenograft model also was used to examine the effect of CHL on the tumor growth and metastasis in vivo. CHL treatment significantly inhibited the proliferation, migration, and invasion ability of both Jurkat and TALL-104 cells and induced cell apoptosis and the expression of miR-9. Moreover, miR-9 was proved to target PD-L1 by binding to its 3′-untranslated region (UTR). Mechanically, pretreated with PD-L1 inhibitor could augment the anti-proliferation and anti-metastatic effect of CHL, while miR-9-silenced alleviated this effect. Consistent with in vitro studies, CHL significantly suppressed the growth and metastasis of tumor in vivo. Our finding uncovers the antitumorigenic effect of CHL in T-ALL progression through upregulating the expression of miR-9 and suppressing PD-L1 expression, which may provide a new potential strategy for T-ALL clinical treatment.