Τίτλος:
Apoptosis induction and gene expression profile alterations of cutaneous T-cell lymphoma cells following their exposure to bortezomib and methotrexate
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL's resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF. Using PCR arrays technology, we also investigated the alterations in the expression profile of genes related to DNA repair pathways in CTCL cell lines after treatment with bortezomib or methotrexate. We found that both agents, but mostly bortezomib, significantly deregulate a large number of genes in SS and MF cell lines, suggesting another pathway through which these agents could induce apoptosis in CTCL. Finally, we show that SS and MF respond differently to treatment, verifying their distinct nature and further emphasizing the need for discrete treatment approaches. © 2017 Mpakou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Συγγραφείς:
Mpakou, V.
Papadavid, E.
Kontsioti, F.
Konsta, E.
Vikentiou, M.
Spathis, A.
Papageorgiou, S.
Vasilatou, D.
Gkontopoulos, K.
Mpazani, E.
Karakitsos, P.
Rigopoulos, D.
Dimitriadis, G.
Pappa, V.
Εκδότης:
Public Library of Science
Λέξεις-κλειδιά:
bortezomib; methotrexate; antineoplastic agent; bortezomib; methotrexate, apoptosis; Article; controlled study; cutaneous T cell lymphoma; DNA repair; drug exposure; flow cytometry; gene expression; human; human cell; lymphoma cell; lymphoma cell line; mycosis fungoides; real time polymerase chain reaction; Sezary syndrome; signal transduction; apoptosis; cutaneous T cell lymphoma; drug effects; gene expression profiling; genetics; pathology; polymerase chain reaction; tumor cell line, Antineoplastic Agents; Apoptosis; Bortezomib; Cell Line, Tumor; DNA Repair; Flow Cytometry; Gene Expression Profiling; Humans; Lymphoma, T-Cell, Cutaneous; Methotrexate; Polymerase Chain Reaction; Signal Transduction
DOI:
10.1371/journal.pone.0170186
