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Selected Publication:
Rohrer, K.
Anti-tumor effects of metabotropic glutamate receptor 1 antagonists on neuroendocrine tumor cell lines
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2014. pp. 72
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- Authors Med Uni Graz:
- Advisor:
- Ghaffari Tabrizi-Wizsy Nassim
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- Abstract:
- Introduction: Small intestinal neuroendocrine tumors (SI-NETs) and medullary thyroid carcinomas (MTC) are counted among the neuroendocrine tumors (NETs). In recent years, the incidence of these tumors has been increasing, but treatment options are still limited. As NETs show low response rates to radiation and chemotherapy, radical surgery still is the only curative therapy option. Glutamate, an excitatory neurotransmitter, plays an important role not only in the central nervous system, but also in peripheral tissues. Glutamate antagonists reduce proliferation of different malignant cells (e.g. melanoma cells, breast cancer cells). In this in vitro study the therapeutic potential of non-competitive, subtype-specific metabotropic glutamate receptor 1 (mGluR1) antagonists in treatment of NETs was analysed. Material and methods: Four SI-NET cell lines (KRJ-I, P-STS, L-STS, H-STS) and two MTC cell lines (MTC-SK, SHER-I) were treated with different concentrations (10- 200 µM) of two mGluR1 antagonists (Cyclothiazide and YM-298198). After 24, 48 or 72 h of incubation, light microscopy, cell counting and analysing as well as analysis of the metabolic cell activity by the WST-1 assay were performed. Additionally, the substances were tested in combination with the chemotherapeutic agent Temozolomide. Results: Both mGluR1 antagonists show dose dependent effects on cell growth and metabolic activity, whereby the dosage of 200 µM was the most effective. The results of the combined treatment with TZM indicate a synergistic effect concerning cell counts and metabolic activity. Furthermore, expression of mGluR1 was detected in all tested cell lines. Conclusion: These data show that mGluR1 antagonists influence growth and metabolism of NET cells. Therefore they could be a new treatment option. This in vitro study builds the basis for further investigations to evaluate the therapeutic potential of mGluR1 antagonists and for a better understanding of the tumor biology of neuroendocrine tumors.