Efficacy and mechanism of the XPO1 inhibitor selinexor combined with decitabine in T-cell lymphoblastic lymphoma.

Abstract

Purpose: T-cell lymphoblastic lymphoma (T-LBL) has a poor response to traditional chemotherapy regimens, and is prone to relapse after treatment. Effective drugs are lacking for relapsed and refractory (RR) T-LBL patients, highlighting the need for novel treatments. Selinexor and decitabine have good effects on a variety of hematolymphatic diseases and solid tumors, but how effective they are in treating T-LBL has not been reported. In this study, we first investigated the efficacy and mechanism of selinexor combined with decitabine in the treatment of T- LBL.

Methods: The proliferation, apoptosis, and cell cycle progression of T-LBL cells were detected via CCK-8 and flow cytometry. Changes in mRNA expression and protein levels were assessed via mRNA sequencing, quantitative real-time PCR, and Western blotting. SLIT2 expression was detected by immunohistochemistry and Western blotting. Tumor xenograft models were established to evaluate the efficacy of drugs in vivo.

Results: Selinexor or decitabine alone inhibited T-LBL cell proliferation in a dose-dependent manner. Cotreatment with both drugs had obvious synergistic effects, promoted cell apoptosis, and induced G0/G1-phase cell cycle arrest in T-LBL cells, and the RNA sequencing results indicated that the tumor suppressor gene SLIT2 might be involved in the synergistic effect of the two drugs. In vivo, this combination showed synergistic antitumor effects in xenograft mouse models.

Conclusions: In summary, selinexor in combination with decitabine has significant synergistic effects both in vitro and in vivo and represents a new treatment option for RR T-LBL.