Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor
Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor
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DOI：
10.1016/j.bbrc.2015.03.178
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发表时间：
2015-05-22
影响因子：
3.1
通讯作者：
Suzuki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Kato, Haruo;Sekine, Yoshitaka;Suzuki, Kazuhiro
二甲双胍是一种双胍类药物，广泛用于治疗2型糖尿病。最近的研究表明，二甲双胍在体外和体内都能抑制癌细胞增殖和肿瘤生长。二甲双胍的抗肿瘤机制包括激活AMP活化蛋白激酶/mTOR通路和直接抑制胰岛素/胰岛素样生长因子（IGF）介导的细胞增殖。然而，前列腺癌的抗肿瘤机制仍不清楚。由于IGF-1受体（IGF-1 R）的激活是前列腺细胞增殖所必需的，因此IGF-1 R抑制剂可能具有治疗价值。因此，我们研究了二甲双胍对前列腺癌细胞中IGF-1 R信号传导的影响。二甲双胍显著抑制PC-3细胞的增殖、迁移和侵袭。IGF-1 R mRNA表达在处理48 h后显著降低，IGF-1 R蛋白表达以类似的方式降低。通过siRNA转染IGF-1 R，可抑制PC-3细胞的增殖、迁移和侵袭。IGF-1激活ERK 1/2和Akt，但二甲双胍治疗减弱了这些作用。此外，二甲双胍腹腔内给药显著降低了PC-3异种移植物中的肿瘤生长和IGF-1 R mRNA表达。我们的研究结果表明，二甲双胍是IGF-1/IGF-1 R系统的有效抑制剂，可能对前列腺癌治疗有益。(C)2015 Elsevier Inc. All rights reserved.
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. (C) 2015 Elsevier Inc. All rights reserved.