Journal
LEUKEMIA RESEARCH
Volume 34, Issue 3, Pages 379-386Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.07.013
Keywords
Lymphoma; Sorafenib; PD184352; MEK1/2/ERK1/2; Mcl-1
Categories
Funding
- National Institutes of Health [CA63753, CA93738, CA100866]
- Leukemia and Lymphoma Society of America [R6059-06]
- Multiple Myeloma Research Foundation
- V Foundation
- Lymphoma SPORE [1P50 CA130805]
Ask authors/readers for more resources
Interactions between the multi-kinase inhibitor sorafenib and MEK1/2 inhibitors were investigated in DLBCL cells. Sorafenib (3-10 mu M) triggered apoptosis in multiple GC and ABC lymphoma cells. Unexpectedly, sorafenib did not cause sustained ERK1/2 inactivation, and in SUDHL-6 and -16 cells, triggered ERK1/2 activation. Marginally toxic MEK1/2 inhibitor concentrations (5 mu M PD184352) abrogated ERK1/2 activation in sorafenib-treated cells and synergistically potentiated apoptosis. MEK1 shRNA transfection also significantly increased sorafenib-mediated lethality. Sorafenib/PD184352 co-administration accelerated Mcl-1 down-regulation without up-regulating Bim(EL). Finally, ectopic Mcl-1 expression attenuated sorafenib/PD184352-mediated apoptosis. Together, these findings provide a theoretical basis for potentiating sorafenib anti-lymphoma activity by MEK1/2 inhibitors. (C) 2010 Published by Elsevier Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available