The anti-lymphoma activity and mechanism(s) of action of the multikinase inhibitor sorafenib were investigated using a panel of lymphoma cell lines, including SU-DHL-4V, Granta-519, HD-MyZ, and KMS-11 cell lines. In vitro, sorafenib significantly decreased cell proliferation and phosphorylation levels of MAPK and PI3K/Akt pathways while increased apoptotic cell death. In vivo, sorafenib treatment resulted in a cytostatic rather than cytotoxic effect on tumor cell growth associated with a limited inhibition of tumor volumes. However, sorafenib induced an average 50% reduction of tumor vessel density and a 2-fold increase of necrotic areas. Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. In conclusion, sorafenib affects the growth of lymphoid cell lines by triggering antiangiogenic mechanism(s) and directly targeting tumor cells.
Sorafenib inhibits lymphoma xenografts by targeting MAPK/ERK and AKT pathways in tumor and vascular cells / C. Carlo-Stella, S.L. Locatelli, A. Giacomini, L. Cleris, E. Saba, M. Righi, A. Guidetti, A.M. Gianni. - In: PLOS ONE. - ISSN 1932-6203. - 8:4(2013), pp. e61603.1-e61603.13.
|Titolo:||Sorafenib inhibits lymphoma xenografts by targeting MAPK/ERK and AKT pathways in tumor and vascular cells|
|Parole Chiave:||MAP kinase signaling System ; angiogenesis inhibitors ; animals ; apoptosis ; cell count ; cell line tumor ; cell proliferation ; cell survival ; endothelial cells ; extracellular signal-regulated MAP kinases ; humans ; lymphoma ; mice ; Mice SCID ; necrosis ; neovascularization pathologic ; niacinamide ; pericytes ; phenylurea compounds ; phosphatidylinositol 3-kinases ; posphorylation ; protein kinase inhibitors ; proto-oncogene proteins c-akt ; xenograft model antitumor assays|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
Settore MED/15 - Malattie del Sangue
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0061603|
|Appare nelle tipologie:||01 - Articolo su periodico|