Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma

摘要: Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of non-Hodgkin and currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options short survival. The greatest challenge improving survival DLBCL patients is overcoming chemo-resistance, whose basis poorly understood. Among potential mediators chemo-resistance thioredxoin (Trx) family, primarily because Trx family members play critical roles regulation cellular redox homeostasis, recent studies have indicated that dysregulated homeostasis also plays a key role chemoresistance. In this study, we showed DLBCL-derived lines primary cells express higher basal levels Trx-1 than normal expression level associated with decreased Our functional inhibition by small interfering RNA or inhibitor (PX-12) inhibited growth, clonogenicity, sensitized to doxorubicin-induced growth vitro. These results indicate survival, well chemoresistance, target overcome drug resistance relapsed/refractory DLBCL.