Figure 1.

Oral administration of metformin together with doxorubicin suppress tumor growth and relapse in breast xenografts. A, Tumor volume (mean ± SD) in mice injected (on day 0) with transformed ER-Src cells, BT-474 cancer cells, and MDA-MB-231 cancer cells that were untreated (NT), treated by intra-tumoral injections (days 10, 15, 20, 25) with 4 mg/kg doxorubicin, treated continuously with metformin in drinking water (200 μg/ml) starting at day 10 or both. Tumor volume was monitored 65 days post injection. B, Percent (mean ± SD) of CD44^high/CD24^low cells (CSCs) derived from tumors derived from the indicated cell lines (day 25) in mice that were untreated, treated with doxorubicin (1 or 4 mg/kg), metformin (200 μg/ml) or both. C, CD44^high/CD24^low cells (CSCs) and CD44^low/CD24^high cells (NSCCs) purified from human mammary adenocarcinomas were treated with metformin (0.1 mmol/L) for 48h or left untreated for the same time. Data is presented as percent cell growth, which is determined by the number of metformin-treated cells divided by the number of non-treated cells at the 48h time point. D, Number of mammospheres per 1000 cells derived from human mammary adenocarcinomas after treatment with metformin (0.1 mmol/L) for 48h.