Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Brauchart, T.
The role of fasting in anti-cancer treatment of aggressive lymphomas.
[ Diplomarbeit/Master Thesis (UNI) ] Graz University of Technology; 2020. pp.82.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Deutsch Alexander
- Feichtinger Julia
- Altmetrics:
- Abstract:
- Background: Diffuse large B cell lymphoma and Burkitt lymphoma belong to the group of non-Hodgkin-lymphomas and represent lymphomas with an aggressive clinical course. The fact, that their incidence is increasing and that one third of patients relapses, indicates the need for novel therapeutic intervention. Tested in different types of cancer i.e. glioblastoma, fasting is becoming an efficient combination tool to enhance the sensibility to chemotherapeutics and to reduce side effects according to the differential stress sensibility and resistance theory. Aims: The aim of this master thesis was to investigate if fasting effects the growth inhibitor activity of the BTK-inhibitor Ibrutinib in aggressive lymphoma cell lines. Furthermore, activation of BCR signalling pathways, especially the NF-κB, PI3K/Akt and MAPK pathway, was studied under fasting conditions. Methods: We fasted two different ABC-DLBCL cell lines (RI-1 and U2932), two GCB-DLBCL cell lines (SuDHL4 and Karpas-422) and two Burkitt lymphoma cell lines (Raji and BL-2) in media with reduced glucose and reduced protein concentration. After pre-fasting for 24h, the cells were treated in a range from 50μM to 0.25μM with Ibrutinib followed by cell growth assay (EZ4U) after 24h, 48h and 72h. In addition, the expression levels of known NF-κB, MAPK and PI3K target genes were determined by RQ-PCR after 24h pre-fasting. In addition, members of the NF-κB pathway were investigated by Western blot analysis. Unfasted cells served as controls. Results: Combining fasting with Ibrutinib treatment significantly increased the cell growth inhibition compared to treatment alone of all investigated lymphoma cell lines (RI-1, U2932, SuDHL4, Karpas-422, Raji and BL-2) after 24h, 48h and 72h. The IC50 concentration was around 1.5-fold lower for fasted cells compared to controls. Furthermore, more cells were stained positive for Annexin V, when fasting and Ibrutinib treatment were combined. Interestingly, most fasted cell lines exhibited higher expression of NF-κB, MAPK and PI3K target genes in comparison to unfasted controls. Finally, Western blot analysis demonstrated that members of the NF-κB pathway were higher induced and/or higher activated by fasting. Conclusion: Our data indicates that fasting potentiates the anticancer activity of Ibrutinib. Fasting seems to potentially activate several pathways linked to BCR signalling and therefore rendering lymphoma cells, making them more vulnerable targets to specific inhibitors. Based on our finding, the combination of dietary intervention with Ibrutinib treatment should be further taken into consideration and be investigated for anticancer therapy of aggressive lymphomas.