Hyperglycaemia-induced resistance to Docetaxel is negated by metformin

New study, -Patrick

ncbi.nlm.nih.gov/pubmed/277...

Endocr Relat Cancer. 2016 Oct 17. pii: ERC-16-0095. [Epub ahead of print]

Hyperglycaemia-induced resistance to Docetaxel is negated by metformin: a role for IGFBP-2.

Biernacka K1, Persad RA2, Bahl A3, Gillatt D4, Holly JM5, Perks CM6.

Author information

Abstract

The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes via targeting this pathway. We investigated the effect of metformin on prostate cancer cell lines and evaluated its mechanism of action using DU145, LNCaP, PC3 and VCaP prostate cancer cell lines. Trypan blue dye-exclusion assay was used to assess levels of cell death. Western immunoblotting was employed to determine abundance of proteins. Insulin-like growth factor binding protein-2(IGFBP-2) and AMPK genes were silenced using siRNA. Effects on cell morphology were visualized using microscopy. IGFBP-2 gene expression was assessed using real-time RT-PCR. With DU145 and LNCaP cells metformin alone induced cell death, but this was reduced in hyperglycaemic. Hyperglycaemia also reduced the sensitivity to Docetaxel but this was countered by co-treatment with metformin. LKB1 was required for the activation of AMPK but was not essential to mediate the induction of cell death. An alternative pathway by which metformin exerted its action was through down-regulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK. This finding could have important implications in relation to therapeutic strategies in prostate cancer patients presenting with diabetes.

PMID: 27754854 DOI: 10.1530/ERC-16-0095

[PubMed - as supplied by publisher]

2 Replies

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  • Patrick,

    What are the implications for treatment for PCa patients with type 2 diabetes?

    Rich

  • patandemma@+pjoshea13

    I thought I did a lot of reading but you are amazing AND you take the time to share.

    You are an MVP contributor to this forum !

    Thank you

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