Seliger, Corinna and Meyer, Anne-Louise and Renner, Kathrin and Leidgens, Verena and Moeckel, Sylvia and Jachnik, Birgit and Dettmer, Katja and Tischler, Ulrike and Gerthofer, Valeria and Rauer, Lisa and Uhl, Martin and Proescholdt, Martin and Bogdahn, Ulrich and Riemenschneider, Markus J. and Oefner, Peter J. and Kreutz, Marina and Vollmann-Zwerenz, Arabel and Hau, Peter (2016) Metformin inhibits proliferation and migration of glioblastoma cells independently of TGF-beta 2. CELL CYCLE, 15 (13). pp. 1755-1766. ISSN 1538-4101, 1551-4005
Full text not available from this repository. (Request a copy)Abstract
To this day, glioblastoma (GBM) remains an incurable brain tumor. Previous research has shown that metformin, an oral anti-diabetic drug, may decrease GBM cell proliferation and migration especially in brain tumor initiating cells (BTICs). As transforming growth factor 2 (TGF-(2)) has been reported to promote high-grade glioma and is inhibited by metformin in other tumors, we explored whether metformin directly interferes with TGF-(2)-signaling. Functional investigation of proliferation and migration of primary BTICs after treatment with metformin+/-TGF-(2) revealed that metformin doses as low as 0.01mM metformin thrice a day were able to inhibit proliferation of susceptible cell lines, whereas migration was impacted only at higher doses. Known cellular mechanisms of metformin, such as increased lactate secretion, reduced oxygen consumption and activated AMPK-signaling, could be confirmed. However, TGF-(2) and metformin did not act as functional antagonists, but both rather inhibited proliferation and/or migration, if significant effects were present. We did not observe a relevant influence of metformin on TGF-(2) mRNA expression (qRT-PCR), TGF-(2) protein expression (ELISA) or SMAD-signaling (Western blot). Therefore, it seems that metformin does not exert its inhibitory effects on GBM BTIC proliferation and migration by altering TGF-(2)-signaling. Nonetheless, as low doses of metformin are able to reduce proliferation of certain GBM cells, further exploration of predictors of BTICs' susceptibility to metformin appears justified.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL-MESENCHYMAL TRANSITION; ACTIVATED PROTEIN-KINASE; HIPPOCAMPAL SLICE CULTURES; GROWTH-FACTOR-BETA; CANCER STEM-CELLS; TGF-BETA; DIABETIC-NEPHROPATHY; PATHWAY-ACTIVITY; GLIOMA INVASION; HIGH GLUCOSE; AMPK; BTIC; glioblastoma; metformin; mTOR; SMAD; TGF-beta(2) |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2019 13:42 |
| Last Modified: | 18 Mar 2019 13:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2670 |
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