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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 the...
Source: Biochemical and Biophysical Research communications - April 7, 2015 Category: Biochemistry Authors: Kato H, Sekine Y, Furuya Y, Miyazawa Y, Koike H, Suzuki K Tags: Biochem Biophys Res Commun Source Type: research

Metformin Enhances Cisplatin Cytotoxicity by Suppressing Stat3 Activity Independently of the LKB1-AMPK Pathway.
This study demonstrated a correlation between Stat3 phosphorylation and cisplatin cytotoxicity using AS2 (PC14PE6/AS2)-derived cell lines (AS2/S3C) that contained constitutively active Stat3 plasmids as a model. A Stat3 inhibitor (JSI-124) enhanced the cisplatin sensitivity in AS2 cells, whereas metformin inhibited Stat3 phosphorylation and enhanced cisplatin cytotoxicity. By contrast, another AMPK activator (AICAR) failed to produce these effects. LKB1-AMPK silencing by siRNA or mTOR inhibition by rapamycin or pp242 did not alter the effect of metformin on Stat3 activity suppression, suggesting that metformin can modulate...
Source: American Journal of Respiratory Cell and Molecular Biology - March 22, 2013 Category: Molecular Biology Authors: Lin CC, Yeh HH, Huang WL, Yan JJ, Lai WW, Su WP, Chen HH, Su WC Tags: Am J Respir Cell Mol Biol Source Type: research

Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.
Abstract Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug. On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC). High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy. In this current study, paclitaxel was found to increase phosphorylati...
Source: Biochemical Pharmacology - December 7, 2012 Category: Drugs & Pharmacology Authors: Tseng SC, Huang YC, Chen HJ, Chiu HC, Huang YJ, Wo TY, Weng SH, Lin YW Tags: Biochem Pharmacol Source Type: research

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