Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study.
Gynecol Oncol
; 143(3): 466-471, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27745917
ABSTRACT
OBJECTIVE:
Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC.METHODS:
In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry.RESULTS:
Twenty patients completed the trial. Median age and BMI were 57years (range 27-67) and 34.5kg/m2 (range 21.9-50.0). Median duration of metformin was 9.5days (range 7-24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035). Compared to baseline, post-treatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p=0.0002), decreased phospho-S6rp in 14/20 patients (70%, p=0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p=0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation.CONCLUSION:
In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Neoplasias do Endométrio
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Carcinoma Endometrioide
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Endométrio
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Hipoglicemiantes
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Metformina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article