Table 2.
Summary of Metformin Effects on the Growth of Human or Mouse Mammary Xenograft/Allograftt Tumors
| Cell Line and Mouse Model (reference) | Metformin Dose (Route of Administration) | Length and/or Aspects of Treatment | Outcome of Metformin Treatment |
|---|---|---|---|
| MDA-MB-435 breast/melanoma cells in female nu/nu mice (36) | 750 mg/kg/day (5000 μg/ml in drinking water) | 12 weeks | Metformin appeared to enhance tumor growth after 5 weeks of treatment. |
| MDA-MB-231 cells in female nu/nu mice (27) | 200 mg/kg/day (2000 μg/ml in drinking water) | Started 8 days after cell inoculation | Tumor growth delayed (p<0.01.) Survived longer with tumors <2 cm in diameter, i.e., 80 vs 35 days Ki67 staining reduced by 100% |
| MDA-MB-231 cells in female nu/nu mice (27) | 200 mg/kg/day (2000 μg/ml in drinking water) | Started 1 week before cell inoculation | Palpable tumors delayed until 20 days after inoculation compared to 10 days for controls Reduced tumor growth 50% tumor incidence vs 100% for controls |
| MCF10A ER-Src cells in female nu/nu mice (35) | 100 μg/mL po | Every 5 days for three cycles | No effect of metformin alone but when combined with doxorubicin no tumor growth. |
| MCF-10A-Src cancer stem cells pretreated with metformin in female nu/nu mice (35) | 0.1 mmol/L in vitro for 0, 24 or 48 h | 20 days after pretreated cells inoculated | Pretreatment prevented tumor formation from these CD44high/CD24low stem cells |
| MCF-10A-ER-Src cells BT-474 cells MDA-MB-231 cells in female nu/nu mice (34) |
200 μg/mL (in drinking water) | 65 days | Tumor volume reduced for all lines for metformin vs. vehicle treated mice by 50% or greater. Stem cells were also affected. |
| MDA-MB-231 cells in female CD-1 nu/nu mice (33) | 250 mg/kg/day (ip) | Started ~ 14 days after cell inoculation tumor 50 mm3 | Tumor weight not affect when mice followed for 35 days- when metformin combined with d-DG significant reduction |
| 78617 Her2/neu mouse cells (30) | Cells implanted after 3 days pretreated with 1 mmol/L met | Tumor volume followed for 14 days. Tumor volume drastically reduced. Expression levels of pErbB2 and pAKT1 reduced. | |
| JIMT-1 HER2 expression and gene amplification in 4–5 week old athymic nude mice (81) | 250 mg/kg/day (ip) | 49 days | 4 groups, control and trastuzumab same tumor size. Metformin reduced more by ~67% and metformin + trastuzumab ~77% |
| MCF10-ER-Src cells in female nu/nu mice (72) | 200 μg/mL(in drinking water) | Started ~ 10 days after cell inoculation ~100mm3 Mice followed for up to 65 days |
6 groups, no treatment, doxorubicin (1 or 4 mg/kg), metformin, or metformin with either of the doxorubicin doses) – metformin alone resulted in reduced tumor growth and also cancer stem cell reduced as well as expression levels of AKT phosphorylation in these cells |
| MMTV-Erbb2 mouse derived cells into 6–9 week old female SCID or FVB/N mice {Orecchioi, 2015 6549/id} | 2 mg/mL (in drinking water) of metformin or 1.65 mg/mL (in drinking water) phenformin | Started 3 days after cell inoculations and followed for 76 days | Tumor volume significantly reduced by both treatments with phenformin more effective. Also a similar effect on lung metastases |
| MDA-MB-436 cells in 6–9 in female SCID mice {Orecchioi, 2015 6549/id} | 2 mg/mL (in drinking water) of metformin or 1.65 mg/mL (in drinking water) phenformin |
Started 3 days after cell inoculations and followed for 67 days | Tumor volume significantly reduced by both treatments with phenformin more effective. Also a similar effect on lung metastases |