ArticleBMC cancer2022
Metformin regulates multiple signaling pathways within castration-resistant human prostate cancer cells.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- Metformin and Flutamide Combination Therapy's Efficacy and Safety in Prostate Cancer Cell Lines.Prostate cancer · 2026Article
- METTL3-mediated mCellular & molecular biology letters · 2024Article
- The Proteomic Analysis of Cancer-Related Alterations in the Human Unfoldome.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe biguanide metformin has been shown to not only reduce circulating glucose levels but also suppress in vitro and in vivo growth of prostate cancer. However, the mechanisms underlying the anti-tumor effects of metformin in advanced prostate cancers are not fully understood. The goal of the present study was to define the signaling pathways regulated by metformin in androgen-receptor (AR) positive, castration-resistant prostate cancers.
methodsOur group used RNA sequencing (RNA-seq) to examine genes regulated by metformin within the C4-2 human prostate cancer cell line. Western blot analysis and quantitative RT-PCR were used to confirm alterations in gene expression and further explore regulation of protein expression by metformin.
resultsData from the RNA-seq analysis revealed that metformin alters the expression of genes products involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum. Gene products involved in ErbB, insulin, mTOR, TGF-β, MAPK, and Wnt signaling pathways are also regulated by metformin. A subset of metformin-regulated gene products were genes known to be direct transcriptional targets of p53 or AR. Western blot analyses and quantitative RT-PCR indicated these alterations in gene expression are due in part to metformin-induced reductions in AR mRNA and protein levels.
conclusionsTogether, our results suggest metformin regulates multiple pathways linked to tumor growth and progression within advanced prostate cancer cells.
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