title: Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo.
abstract: 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.
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia. aging@mail.ru
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Anisimov
authors.forename: Peter A
authors.initials: PA
authors.lastname: Egormin
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Piskunova
authors.forename: Irina G
authors.initials: IG
authors.lastname: Popovich
authors.forename: Margarita L
authors.initials: ML
authors.lastname: Tyndyk
authors.forename: Maria N
authors.initials: MN
authors.lastname: Yurova
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zabezhinski
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Anikin
authors.forename: Arseniy S
authors.initials: AS
authors.lastname: Karkach
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Romanyukha
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000367:Age Factors; D000818:Animals; D005260:Female; D008136:Longevity / Q000187:drug effects; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000502:physiology*
chemical_list: D008550:Melatonin; D008687:Metformin; D018719:Erb-b2 Receptor Tyrosine Kinases