期刊
CELL CYCLE
卷 9, 期 1, 页码 188-197出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.1.10407
关键词
metformin; melatonin; biomarkers of aging; life extension; spontaneous carcinogenesis; transplantable tumors; mice
类别
资金
- Russian Foundation for Basic Research [08-04-0016]
Population studies have shown that treatment with the antidiabetic biguanide metformin significantly reduced cancer risk. In our animal studies, metformin delayed the onset of mammary adenocarcinoma (MAC) in transgenic HeR-2/neu mice but not the onset of spontaneous mammary tumors in female SHR mice. pineal hormone also inhibits mammary carcinoma development in HeR2/neu transgenic mice as well as in female SHR mice. Here we demonstrated that a combination of metformin and melatonin significantly inhibits growth of transplanted tumors in mice. Metformin (0.5 mg/ml in drinking water) increased mean life span by 8% and MAC latency by 13.2% (p < 0.05) in HER2/neu mice. The treatment with melatonin alone (2 mg/L in drinking water during the night time) or combined treatment with metformin (0.5 mg/ml in drinking water during the day time) + melatonin (2 mg/L in drinking water during the night time) did not influence mammary carcinogenesis in the mice. the treatment metformin alone inhibited the growth of transplantable HeR2 mammary carcinoma in FVB/N male mice by 46% at the 45(th) day after transplantation (p < 0.001). the combined treatment with metformin + melatonin significantly suppressed Ehrlich tumor growth (by 40%, p < 0.001). These results suggest that metformin may be useful in prevention and treatment of breast cancer.
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