PDF(Pubmed)
Abstract：
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.
摘要：
原发性中枢神经体系淋巴瘤（PCNSL）是一种罕见的侵袭性脑淋巴瘤，预后较差。使用PCNSL建立的细胞系的稀缺性使得难以对新药进行临床前研究。我们旨在使用已建立的PCNSL细胞和原位PCNSL模型，探讨selinexor联合zanubrutinib在PCNSL中的作用。成功培养原代PCNSL细胞。Selinexor抑制增殖，诱导G1期停滞，并促进细胞凋亡，然而,诱导PCNSL耐药。Selinexor联合zanubrutinib对PCNSL具有协同作用，并通过抑制AKT信号传导来预防PCNSL中selinexor耐药性的发生。此外，与对照组相比，selinexor联合zanubrutinib显着减缓了肿瘤的生长并延长了生存期。总的来说,在selinexor单治疗中加入zanubrutinib在体外具有协同作用,并延长了体内生存期.
