Research Papers:

Metformin potentiates rapamycin and cisplatin in gastric cancer in mice

Guanzhen Yu _, Wenzhang Fang, Tian Xia, Ying Chen, Yunshu Gao, Xiaodong Jiao, Suyun Huang, Zhaosheng Li, Jiejun Wang and Keping Xie

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Oncotarget. 2015; 6:12748-12762. https://doi.org/10.18632/oncotarget.3327

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Guanzhen Yu1,2,*, Wenzheng Fang1,7,*, Tian Xia3,6,*, Ying Chen4,*, Yunshu Gao5, Xiaodong Jiao1, Suyun Huang2, Jiejun Wang1, Zhaosheng Li3, Keping Xie6

1Department of Medical Oncology, Changzheng Hospital, Shanghai 200070, China

2Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

3Department of Gastroenterology, Changhai Hospital, Shanghai 200433, China

4Department of Pathology, Changhai Hospital, Shanghai 200433, China

5Department of Oncology, Qingdao, Shandong 266000, China

6Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

7Department of Oncology, Fuzhou General Hospital, Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, China

*These authors have contributed equally to this work

Correspondence to:

Guanzhen Yu, e-mail: [email protected]

Zhaosheng Li, e-mail: [email protected]

Keping Xie, e-mail: [email protected]

Keywords: gastric cancer, experimental therapy, metformin, mouse model, gene expression

Received: December 26, 2014     Accepted: February 09, 2015     Published: March 25, 2015


Here we showed that pAMPKα and PTEN were down-regulated and p-mTOR, p-S6, p-4EBP1, MMP7, and DCN1 were up-regulated in human gastric cancer tissue samples as compared to that in the noncancerous tissues. Metformin inhibited tumor growth in mice. Also it enhanced cisplatin- or rapamycin-induced reduction of tumor growth as compared with treatment of either drug alone. In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1. We suggest that metformin could potentially be used for the treatment of gastric cancer especially in combination with cisplatin or rapamycin.

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