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Biochem Biophys Res Commun. 2015 May 22;461(1):115-21. doi: 10.1016/j.bbrc.2015.03.178. Epub 2015 Apr 7.

Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor.

Author information

1
Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. Electronic address: hal.kato@gunma-u.ac.jp.
2
Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Abstract

Metformin is a biguanide drug that is widely used for the treatment of type 2 diabetes. Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo. The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF-1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of therapeutic value. Accordingly, we examined the effects of metformin on IGF-1R signaling in prostate cancer cells. Metformin significantly inhibited PC-3 cell proliferation, migration, and invasion. IGF-1R mRNA expression decreased significantly after 48 h of treatment, and IGF-1R protein expression decreased in a similar manner. IGF-1R knockdown by siRNA transfection led to inhibited proliferation, migration and invasion of PC-3 cells. IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment. In addition, intraperitoneal treatment with metformin significantly reduced tumor growth and IGF-1R mRNA expression in PC-3 xenografts. Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment.

KEYWORDS:

IGF-1 receptor; Metformin; PC-3; Prostate cancer

PMID:
25862373
DOI:
10.1016/j.bbrc.2015.03.178
[Indexed for MEDLINE]

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