Abstract
The addition of rituximab (RTX) to standard chemotherapy has improved the treatment of B-cell malignancies. We show here that RTX and dexamethasone (Dex) induced synergistic apoptosis in follicular lymphoma cell lines. However, apoptosis was delayed by RTX-induced early protective signaling. RTX-induced early signaling also decreased Dex-induced apoptosis and led to phosphorylation of ERK1/2, Bcl-2 (at serine 70) and phosphorylation/degradation of BimL/EL. All these events were prevented by the MEK inhibitor, UO126. Therefore, we suggest that RTX-induced ERK-mediated signaling events lead to protection from apoptosis during early signaling and that blocking of Bim and Bcl-2 phosphorylation might be used as a novel strategy for lymphoma treatment.
Acknowledgements
We gratefully acknowledge Eila Pelkonen and Riitta Korhonen for their technical assistance. This work was supported by grants from the Research Committee of the Kuopio University Hospital Catchment Area (State Research Funding), North-Savo cancer organization and Doctoral of Molecular Medicine of University of Eastern Finland.
Potential conflict of interest
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Supplementary material available online
Supplementary Figures 1–4 showing further data.