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- W2000822564 abstract "Development of resistance to the CHOP chemotherapeutic regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) remains a major cause of treatment failure and mortality in approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL). We established CHOP-resistant DLBCL cells as a model system to investigate molecular mechanisms involved in multidrug resistance. Two-dimensional differential in-gel (DIGE) analysis identified 10 differentially expressed proteins between CHOP-sensitive and -resistant DLBCL cells that play roles in glycolysis (triosephosphate isomerase-1, enolase-1), cytoskeletal structure (ezrin, vimentin, tubulin-specific chaperone B), purine biosynthesis (serine hydroxymethyltransferase), calcium binding (sorcin), and apoptosis (p53, 14-3-3ζ, Akt). Akt, 14-3-3ζ, and vimentin were up-regulated in CHOP-resistant DLBCL cells. We showed previously that siRNA-mediated knockdown of 14-3-3ζ reversed CHOP resistance in DLBCL cells (Maxwell et al., J Biol Chem 2009;284:22379-22389). Here we show that chemical inhibition of Akt overcomes CHOP resistance in DLBCL cells. CHOP-resistant cells exhibited a five-fold greater ability to invade collagen matrices compared with CHOP-sensitive cells. Knockdown of vimentin by siRNA or withaferin A repressed the invasiveness of CHOP-resistant cells in collagen matrices. Increased expressions of Akt, 14-3-3ζ, and vimentin were observed by Western blotting in primary DLBCL tissues relative to normal lymphatic tissue. The data implicate activation of an Akt-14-3-3ζ signaling pathway in promoting a multidrug-resistant phenotype associated with a vimentin-dependent invasive behavior in DLBCL cells." @default.
- W2000822564 created "2016-06-24" @default.
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- W2000822564 creator A5032076733 @default.
- W2000822564 creator A5053289507 @default.
- W2000822564 date "2011-02-16" @default.
- W2000822564 modified "2023-10-06" @default.
- W2000822564 title "Akt, 14-3-3ζ, and vimentin mediate a drug-resistant invasive phenotype in diffuse large B-cell lymphoma" @default.
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- W2000822564 doi "https://doi.org/10.3109/10428194.2010.551793" @default.
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