Effect and molecular mechanism of proteasome inhibitor in TRAIL-induced apoptosis resistance on malignant lymphoma cells

Abstract

Objective To explore the effect and molecular mechanism of proteasome inhibitor in TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis resistance on malignant lymphoma cells.Methods Raji cells were treated with TRAIL and proteasome inhibitor (PS-341) in vitro and the cell growth index was evaluated by MTT assay; cell cycle was analysed by flow cytometry; the protein and mRNA level of Bax were measured by Western blotting and real time RT-PCR. Results TRAIL inhibited proliferation of Raji cells at the concentration of 500 μg/L, but the inhibition rate was lower than that of the control cell:Hmy2.ciR.TRAIL arrested cell in G0/G1 phase. The Bax protein in Raji is degraded, but the Bax mRNA expression level does not change significantly .The effects of TRAIL was enhanced significantly 10 nmol/L PS-341 was added. Conclusion Raji cells are resistant in TRAIL-induced apoptosis. This effect may be related to the decrease of Bax protein. The Ubiquitin-proteasome pathway is involved in the degradation of Bax in TRAIL-treated Raji cells. Key words: TRAIL; PS-341; Lymphoma cells; Apoptotic resistance