title: Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor.
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.
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. Electronic address: hal.kato@gunma-u.ac.jp.
authors: Haruo
authors: H
authors: Kato
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Yoshitaka
authors: Y
authors: Sekine
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Yosuke
authors: Y
authors: Furuya
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Yoshiyuki
authors: Y
authors: Miyazawa
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Hidekazu
authors: H
authors: Koike
authors: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Kazuhiro
authors: K
authors: Suzuki
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I; D008687:Metformin; D017526:Receptor, IGF Type 1
keywords: IGF-1 receptor; Metformin; PC-3; Prostate cancer