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The effect of metformin on apoptosis in a breast cancer presurgical trial
BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance sta...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844911/ https://www.ncbi.nlm.nih.gov/pubmed/24157825 http://dx.doi.org/10.1038/bjc.2013.657 |
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author | Cazzaniga, M DeCensi, A Pruneri, G Puntoni, M Bottiglieri, L Varricchio, C Guerrieri-Gonzaga, A Gentilini, O D Pagani, G Dell'Orto, P Lazzeroni, M Serrano, D Viale, G Bonanni, B |
author_facet | Cazzaniga, M DeCensi, A Pruneri, G Puntoni, M Bottiglieri, L Varricchio, C Guerrieri-Gonzaga, A Gentilini, O D Pagani, G Dell'Orto, P Lazzeroni, M Serrano, D Viale, G Bonanni, B |
author_sort | Cazzaniga, M |
collection | PubMed |
description | BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2–12; placebo arm: +2%, IQR: 0–8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2–14 vs +2%, IQR: 0–7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0–6, vs +5%, IQR: 0–15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status. |
format | Online Article Text |
id | pubmed-3844911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38449112014-11-26 The effect of metformin on apoptosis in a breast cancer presurgical trial Cazzaniga, M DeCensi, A Pruneri, G Puntoni, M Bottiglieri, L Varricchio, C Guerrieri-Gonzaga, A Gentilini, O D Pagani, G Dell'Orto, P Lazzeroni, M Serrano, D Viale, G Bonanni, B Br J Cancer Clinical Study BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2–12; placebo arm: +2%, IQR: 0–8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2–14 vs +2%, IQR: 0–7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0–6, vs +5%, IQR: 0–15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status. Nature Publishing Group 2013-11-26 2013-10-24 /pmc/articles/PMC3844911/ /pubmed/24157825 http://dx.doi.org/10.1038/bjc.2013.657 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Clinical Study Cazzaniga, M DeCensi, A Pruneri, G Puntoni, M Bottiglieri, L Varricchio, C Guerrieri-Gonzaga, A Gentilini, O D Pagani, G Dell'Orto, P Lazzeroni, M Serrano, D Viale, G Bonanni, B The effect of metformin on apoptosis in a breast cancer presurgical trial |
title | The effect of metformin on apoptosis in a breast cancer presurgical trial |
title_full | The effect of metformin on apoptosis in a breast cancer presurgical trial |
title_fullStr | The effect of metformin on apoptosis in a breast cancer presurgical trial |
title_full_unstemmed | The effect of metformin on apoptosis in a breast cancer presurgical trial |
title_short | The effect of metformin on apoptosis in a breast cancer presurgical trial |
title_sort | effect of metformin on apoptosis in a breast cancer presurgical trial |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844911/ https://www.ncbi.nlm.nih.gov/pubmed/24157825 http://dx.doi.org/10.1038/bjc.2013.657 |
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