Metformin inhibits proliferation and migration of glioblastoma cells independently of TGF-β2.

作者: Corinna Seliger , Anne-Louise Meyer , Kathrin Renner , Verena Leidgens , Sylvia Moeckel

DOI: 10.1080/15384101.2016.1186316

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摘要: ABSTRACTTo this day, glioblastoma (GBM) remains an incurable brain tumor. Previous research has shown that metformin, oral anti-diabetic drug, may decrease GBM cell proliferation and migration especially in tumor initiating cells (BTICs). As transforming growth factor β 2 (TGF-β2) been reported to promote high-grade glioma is inhibited by metformin other tumors, we explored whether directly interferes with TGF-β2-signaling. Functional investigation of primary BTICs after treatment metformin+/−TGF-β2 revealed doses as low 0.01 mM thrice a day were able inhibit susceptible lines, whereas was impacted only at higher doses. Known cellular mechanisms such increased lactate secretion, reduced oxygen consumption activated AMPK-signaling, could be confirmed. However, TGF-β2 did not act functional antagonists, but both rather ...

参考文章(61)
Roberto Würth, Alessandra Pattarozzi, Monica Gatti, Adirana Bajetto, Alessandro Corsaro, Alessia Parodi, Rodolfo Sirito, Michela Massollo, Cecilia Marini, Gianluigi Zona, Daniela Fenoglio, Gianmario Sambuceti, Gilberto Filaci, Antonio Daga, Federica Barbieri, Tullio Florio, Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt. Cell Cycle. ,vol. 12, pp. 145- 156 ,(2013) , 10.4161/CC.23050
Xiao-Yan Zhao, Ling Li, Xiao-Fang Wang, Jin-Ying Zhang, Beneficial effects of metformin on primary cardiomyocytes via activation of adenosine monophosphate-activated protein kinase. Chinese Medical Journal. ,vol. 124, pp. 1876- 1884 ,(2011)
Marta Gritti, Roberto Würth, Marina Angelini, Federica Barbieri, Marta Peretti, Erika Pizzi, Alessandra Pattarozzi, Elisa Carra, Rodolfo Sirito, Antonio Daga, Paul M.G. Curmi, Michele Mazzanti, Tullio Florio, Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current Oncotarget. ,vol. 5, pp. 11252- 11268 ,(2014) , 10.18632/ONCOTARGET.2617
Karl Frei, Dorothee Gramatzki, Isabel Tritschler, Judith Johanna Schroeder, Larisa Espinoza, Elisabeth Jane Rushing, Michael Weller, None, Transforming growth factor-β pathway activity in glioblastoma. Oncotarget. ,vol. 6, pp. 5963- 5977 ,(2015) , 10.18632/ONCOTARGET.3467
J. P. Annes, Making sense of latent TGFβ activation Journal of Cell Science. ,vol. 116, pp. 217- 224 ,(2003) , 10.1242/JCS.00229
Zhiyun Yu, Gang Zhao, Guifang Xie, Liyan Zhao, Yong Chen, Hongquan Yu, Zhonghua Zhang, Cai Li, Yunqian Li, Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo Oncotarget. ,vol. 6, pp. 32930- 32943 ,(2015) , 10.18632/ONCOTARGET.5405
Gwon-Soo Jung, Jae-Han Jeon, Yeon-Kyung Choi, Se Young Jang, Soo Young Park, Mi-Kyung Kim, Eui-Cheol Shin, Won-Il Jeong, In-Kyu Lee, Yu Na Kang, Keun-Gyu Park, Small heterodimer partner attenuates profibrogenic features of hepatitis C virus-infected cells. Liver International. ,vol. 35, pp. 2233- 2245 ,(2015) , 10.1111/LIV.12871
Justin D. Lathia, Stephen C. Mack, Erin E. Mulkearns-Hubert, Claudia L.L. Valentim, Jeremy N. Rich, Cancer stem cells in glioblastoma Genes & Development. ,vol. 29, pp. 1203- 1217 ,(2015) , 10.1101/GAD.261982.115
Katja Dettmer, Pavel A. Aronov, Bruce D. Hammock, Mass spectrometry-based metabolomics. Mass Spectrometry Reviews. ,vol. 26, pp. 51- 78 ,(2007) , 10.1002/MAS.20108
Julie Sesen, Perrine Dahan, Sarah J. Scotland, Estelle Saland, Van-Thi Dang, Anthony Lemarié, Betty M. Tyler, Henry Brem, Christine Toulas, Elizabeth Cohen-Jonathan Moyal, Jean-Emmanuel Sarry, Nicolas Skuli, Metformin Inhibits Growth of Human Glioblastoma Cells and Enhances Therapeutic Response PLOS ONE. ,vol. 10, pp. e0123721- ,(2015) , 10.1371/JOURNAL.PONE.0123721