L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells

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• 作者：José Mendes ; Ana Cristina Gonçalves ; Raquel Alves…
• 关键词：Diffuse Large B ; cell Lymphoma ; Burkitt’s lymphoma ; Everolimus ; L744 ; 832 ; Apoptosis
• 刊名：Pathology & Oncology Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：22
• 期：2
• 页码：301-309
• 全文大小：1,199 KB
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• 作者单位：José Mendes (1)
  Ana Cristina Gonçalves (1) (2) (3)
  Raquel Alves (1) (2) (3)
  Joana Jorge (1) (2)
  Ana Pires (1) (2)
  Ana Ribeiro (1)
  Ana Bela Sarmento-Ribeiro (1) (2) (3) (4)
  
  1. University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine University of Coimbra – FMUC, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal
  2. Center of Investigation on Environment Genetic and Oncobiology – CIMAGO, FMUC, Coimbra, Portugal
  3. Center for Neuroscience and Cell Biology – CNC.IBILI, University of Coimbra, Coimbra, Portugal
  4. Clinical Hematology Department, Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal
  
• 刊物主题：Cancer Research; Oncology; Pathology; Immunology; Biomedicine general;
• 出版者：Springer Netherlands
• ISSN：1532-2807

文摘

Non-Hodgkin Lymphoma (NHL) constitutes a very heterogeneous group of diseases with different aggressiveness. Diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) are two clinically aggressive lymphomas from the germinal center, very heterogeneous and with different genetic signatures. Several intracellular pathways are involved in lymphomagenesis, being BCR/PI3K/AKT/mTOR and RAS/RAF pathways the most frequently ones. In this context the therapeutic potential of a mTOR inhibitor – everolimus – and a RAS/RAF pathway inhibitor – L744,832 – was evaluated in two NHL cell lines. Farage and Raji cells were cultured in the absence and presence of several concentrations of everolimus and L744,832 in monotherapy and in combination with each other, as well as in association with the conventional chemotherapy drug vincristine. Our results show that everolimus and L744,832 induce antiproliferative and cytotoxic effect in a time-, dose-, and cell line-dependent manner, inducing cell death mainly by apoptosis. A potentiation effect was observed when the drugs were used in combination. In conclusion, the results suggest that everolimus and L744,832, alone or in combination, could provide therapeutic benefits in these subtypes of NHL.