Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

被引：192

作者：

Fendt, Sarah-Maria ^{[1
]}

Bell, Eric L. ^{[2
]}

Keibler, Mark A. ^{[1
]}

Davidson, Shawn M. ^{[2
,3
]}

Wirth, Gregory J. ^{[4
]}

Fiske, Brian ^{[2
,3
]}

Mayers, Jared R. ^{[2
,3
]}

Schwab, Matthias ^{[10
,11
,12
]}

Bellinger, Gary ^{[5
]}

Csibi, Alfredo ^{[7
]}

Patnaik, Akash

Blouin, Marie Jose

Cantley, Lewis C. ^{[5
,6
]}

Guarente, Leonard ^{[2
]}

Blenis, John

Pollak, Michael N. ^{[9
]}

Olumi, Aria F. ^{[4
]}

Vander Heiden, Matthew G. ^{[2
,3
,8
]}

Stephanopoulos, Gregory ^{[1
]}

机构：

[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA

[4] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA

[5] Beth Israel Deaconess Canc Ctr, Div Signal Transduct, Dept Med, Boston, MA USA

[6] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA

[7] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA

[8] Dana Farber Canc Inst, Boston, MA 02115 USA

[9] McGill Univ, Dept Oncol, Montreal, PQ, Canada

[10] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada

[11] Doctor Margarete Fischer Bosch Inst Clin Pharmaco, Stuttgart, Germany

[12] Univ Hosp, Inst Expt & Clin Pharmacol & Toxicol, Dept Clin Pharmacol, Tubingen, Germany

来源：

CANCER RESEARCH | 2013年 / 73卷 / 14期

关键词：

INHIBITION; RISK; FLUX; PROLIFERATION; APOPTOSIS; BIOLOGY; ARREST; GROWTH; EMU;

D O I：

10.1158/0008-5472.CAN-13-0080

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer. (C) 2013 AACR.

引用

页码：4429 / 4438

页数：10

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