The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

作者: Mi-Ae Lyu , Deepak Rai , Kwang Seok Ahn , Bokyung Sung , Lawrence H. Cheung

DOI: 10.1593/NEO.91960

关键词: In vivoLymphomaFusion ToxinB-cell activating factorDiffuse large B-cell lymphomaSurvivinCell growthMolecular biologyBiologyCytotoxic T cell

摘要: Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin (NHL) and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB) are expected to be therapeutic value in those tumors where NF-κB seems play a unique survival role such as activated (ABC)-subtype DLBCL. We previously generated rGel/BLyS fusion toxin receptor-mediated delivery the rGel specifically malignant B cells. In this study, we examined its ability suppress DLBCL growth vitro vivo. was cytotoxic lines expressing all three BLyS receptors constitutively active NF-κB. Treatment with induced down-regulation phosphorylation inhibitory subunit (IκB-α), inhibition DNA-binding activity, accumulation IκB-α. agreement these results, additionally found that downregulated levels several targets including Bcl-xL, Mcl-1, survivin, x-chromosome linked inhibitor-of-apoptosis. also up-regulation Bax apoptosis through caspase-3 activation poly ADP-ribose polymerase cleavage. Importantly, significantly inhibited tumor (P < .05) xenograft model. Thus, our results indicate excellent candidate treatment NHLs both dependent on resistant conventional chemotherapeutic regimens.

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