We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Measuring the biological effect of presurgical metformin treatment in endometrial cancer.
- Authors
Sivalingam, V N; Kitson, S; McVey, R; Roberts, C; Pemberton, P; Gilmour, K; Ali, S; Renehan, A G; Kitchener, H C; Crosbie, E J
- Abstract
<bold>Background: </bold>Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. We tested the hypothesis that short-term presurgical metformin reduces cellular proliferation in atypical endometrial hyperplasia (AEH) and endometrioid EC, and assessed the feasibility of using phosphorylated PI3K-AKT-mTOR proteins as tissue end points.<bold>Methods: </bold>Women with AEH or EC received metformin 850 mg twice a day or no drug in the presurgical window between diagnosis and hysterectomy. Before and after the window, tissue samples were obtained; serum markers of insulin resistance (e.g. homeostasis model of assessment of insulin resistance index) were determined; and anthropometrics measured (e.g. BMI). Cell proliferation (Ki-67) and PI3K-AKT-mTOR phosphostatus were assessed by immunohistochemistry and scored blinded to treatment.<bold>Results: </bold>Twenty-eight metformin-treated and 12 untreated patients, well matched for age and BMI, completed the study. Metformin treatment (median 20 days, range 7-34) was associated with a 17.2% reduction in tumour Ki-67 (95% CI -27.4, -7.0, P=0.002), in a dose-dependent manner. Tumour PI3K-AKT-mTOR protein phosphostatus varied but the effects were not significant after adjusting for changes in controls.<bold>Conclusions: </bold>Short-term metformin was associated with reduced Ki-67 expression in EC. Changes in tumour PI3K-AKT-mTOR protein phosphostatus were seen in both groups. Future studies should address the variability attributed to different sampling techniques including devascularisation of the uterus at hysterectomy.
- Subjects
HYPOGLYCEMIC agents; METFORMIN; BLOOD sugar; C-peptide; CANCER invasiveness; CLINICAL trials; COMBINED modality therapy; COMPARATIVE studies; ENZYME-linked immunosorbent assay; HYSTERECTOMY; IMMUNOHISTOCHEMISTRY; INSULIN; INSULIN resistance; RESEARCH methodology; MEDICAL cooperation; MYOMETRIUM; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PREOPERATIVE care; RESEARCH; RESEARCH funding; TRANSFERASES; TUMOR markers; UTERINE diseases; ENDOMETRIAL tumors; EVALUATION research; TREATMENT effectiveness; TUMOR grading
- Publication
British Journal of Cancer, 2016, Vol 114, Issue 3, p281
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2015.453