The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo
| Autor: | Stefanie Schrauwen, Frédéric Amant, Diether Lambrechts, Anna Cattaneo, Lieve Coenegrachts, Els Hermans |
|---|---|
| Přispěvatelé: | Other departments |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
medicine.medical_specialty endocrine system diseases Mice Nude Carboplatin Mice chemistry.chemical_compound In vivo Internal medicine Antineoplastic Combined Chemotherapy Protocols Carcinoma medicine Animals Humans PI3K/AKT/mTOR pathway business.industry Endometrial cancer nutritional and metabolic diseases Obstetrics and Gynecology AMPK Cancer medicine.disease Xenograft Model Antitumor Assays Metformin Endometrial Neoplasms chemistry Cancer research Female business Carcinoma Endometrioid medicine.drug |
| Zdroj: | Gynecologic oncology, 138(2), 378-382. Academic Press Inc. |
| ISSN: | 0090-8258 |
| Popis: | Objectives. New treatment options for advanced and recurrent endometrial carcinoma (EC) are necessary. Epidemiological studies showed that diabetic patients using metformin have reduced risks of endometrial cancer (EC) incidence. Moreover, pre- and clinical studies demonstrated an antitumor effect by metformin, with and without additional treatments, for different solid malignancies. However, cancer cell-autonomous effects of metformin on EC have not been fully characterized yet. The aim of this study was to investigate the effect of metformin, with or without carboplatin, on patient-derived primary endometrioid EC cells xenografted in nude mice, to assess its ability to reduce or impair growth in already established tumors. Methods. Two xenograft models were established by subcutaneous inoculation of primary endometrioid EC cell suspensions. Tumors were allowed to grow and then mice were treated with metformin (250 mg/kg, daily, p.o.), carboplatin (50 mg/kg, 1 x/week, i.p.), or the combination of both compounds at the same concentration as single treatment, for three weeks. Effects of metformin treatment on the tumor mass were determined by tumor growth follow-up. Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels. Results. In vivo, metformin did not affect the growth of EC tumors established from patient-derived primary cultures and the phosphorylation of ART, AMPK and S6. In addition, no enhanced antitumor effect was determined by combining metformin and carboplatin treatments. Conclusions. Metformin, at clinically relevant concentrations, did not show effects on the growth of already established tumors. Adding metformin to carboplatin did not have synergistic effects. (C) 2015 Elsevier Inc. All rights reserved |
| Databáze: | OpenAIRE |
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