Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gams, P.
Influence of the proteasome inhibitor bortezomib on cell cycle distribution of human synovial sarcoma cells
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. 65
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Lohberger Birgit
- Altmetrics:
- Abstract:
- A synovial sarcoma is an aggressive malignant tumor with a pronounced tendency for local recurrence and metastasis. With an incidence of 2-4/100000 it represents the fourth most common malignant soft tissue tumor and occurs, with an average disease age of 35 years, preferably in younger patients. The use of chemotherapeutic agents, often only shows moderate success and is limited by side effects. The currently poor prognosis is based on the usually late diagnosis position on the one hand and on the limited therapeutic possibilities on the other. Therefore, it is essential to find new, more effective substances to enhance the therapeutic options and to improve the prognosis of the patients. The drug bortezomib from the substance class of proteasome inhibitors may represent such a substance. The current approval is limited to a few specific, malignant haematological disorders. However, numerous studies have already demonstrated an antineoplastic effect even on solid tumors. The effects of bortezomib on synovial sarcoma cells are still widely unexplored. In this study, it is clearly shown that Bortezomib inhibits, depending on the concentration, the proliferation rate, the growth behavior as well as the viability of synovial carcinoma cells (SW-982). Based on collected flow cytometry data, cell accumulation was observed in G2-phase. The measured results lead to the conclusion that bortezomib drives synovial carcinoma cells into a G2/M arrest. The expression of certain genes under the influence of bortezomib was determined by rt-qPCR. At a concentration of 10 nM (IC50), a statistically significant decrease of CDK2 was detected after 48 hours. The collected data indicates that bortezomib can also express its anti-carcinogenic effect in synovial sarcoma cells. Further the study shows that bortezomib has the requirements to complement future therapies. Overall more information must be generated and therefore further in-vitro and in-vivo studies are needed to examine the effect of bortezomib in more detail.