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The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo.

Abstract：

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×/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 AKT, 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.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Schrauwen S,Coenegrachts L,Cattaneo A,Hermans E,Lambrechts D,Amant F

doi

10.1016/j.ygyno.2015.06.006

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

378-82

issue

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(15)30027-5

journal_volume

138

pub_type

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The antitumor effect of metformin with and without carboplatin on primary endometrioid endometrial carcinoma in vivo.