Title |
The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo
|
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Published in |
Gynecologic Oncology, June 2015
|
DOI | 10.1016/j.ygyno.2015.06.006 |
Pubmed ID | |
Authors |
Stefanie Schrauwen, Lieve Coenegrachts, Anna Cattaneo, Els Hermans, Diether Lambrechts, Frédéric Amant |
Abstract |
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 has 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. 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 (250mg/kg, daily, p.o.), carboplatin (50mg/kg, 1x/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 was evaluated by investigating AKT, AMPK and S6 phosphorylation levels. In vivo, metformin did not affect the growth of EC tumors established from patient-derived primary cultures and the phosphorylation of AKT, AMPK and S6. In addition, no enhanced antitumor effect was determined by combining metformin and carboplatin treatments. 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. |
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Demographic breakdown
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Student > Ph. D. Student | 6 | 22% |
Researcher | 4 | 15% |
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Student > Doctoral Student | 1 | 4% |
Other | 2 | 7% |
Unknown | 6 | 22% |
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Nursing and Health Professions | 2 | 7% |
Other | 0 | 0% |
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