Análisis de la respuesta de un inhibidor de PI3K en modelo celular Raji

Díaz-Tejeiro Rodríguez, Cristina (2019). Análisis de la respuesta de un inhibidor de PI3K en modelo celular Raji. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Análisis de la respuesta de un inhibidor de PI3K en modelo celular Raji
Author/s:
  • Díaz-Tejeiro Rodríguez, Cristina
Contributor/s:
  • Sánchez-Beato Gómez, Margarita
  • Ramírez Castillejo, María del Carmen
Item Type: Final Project
Degree: Grado en Biotecnología
Date: June 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Lymphomas are a group of neoplasms of the lymphatic system. The disease arises from malignant transformation of B and T cells. Lymphomas can be divided into two types: Hodgkin lymphomas (HL) and Non-Hodgkin lymphomas (NHL). NHL represents around 90% of all lymphomas and, in general terms, have worse prognosis than HL. Most NHL are B cell lymphomas (B-NHL), which means the disease starts in B lymphocytes. Some B-NHL can be aggressive, so the tumor proliferates very fast. The standard treatment for these B cell lymphomas is immunochemotherapy with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Nowadays, the main problem in aggressive B-cell lymphomas is the resistance to this therapy. Treatments with targeted therapies, such as phosphoinositide 3-kinase (PI3K) inhibitors, could be alternative treatments for refractory patients to R-CHOP, as demonstrated by ongoing clinical trials. However, more research is needed to understand the mechanisms of sensitivity / resistance to these inhibitors and to identify patients likely to be treated with them. Therefore, the aim of this study is to characterize the molecular mechanisms of response to treatment with a PI3K inhibitor (PI3Ki) in rituximab-sensitive and resistant model using Raji cell line, which is derived from a Burkitt's lymphoma (aggressive B-NHL). The effect of the PI3K inhibitor on proliferation and protein signaling was studied using flow cytometry for cell cycle and apoptosis, and western blot to analyze its effect on proteins of the PI3K pathway. With our results, we conclude that the addition of the drug stops cell proliferation. The PI3Ki blocks cell cycle in G1, as well as increases apoptosis. This was supported by changes in phosphorylation levels of PI3K pathway-proteins that regulate cell proliferation and apoptosis: GSK-3 and BAD. Also, when analyzing the PI3K p110 complex before and after PI3Ki addition, we observed that the p110δ isoform was an important target in these neoplasms, because it was the most expressed. We also observed that in the Raji cell, the PI3K route did not seem to be mediated by AKT, but by alternative routes.

More information

Item ID: 57480
DC Identifier: http://oa.upm.es/57480/
OAI Identifier: oai:oa.upm.es:57480
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 11 Dec 2019 12:31
Last Modified: 11 Dec 2019 12:31
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