title: Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.
abstract: Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Guo
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Li
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Sheng-Yan
authors.initials: SY
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Wang
authors.forename: Jing-Miao
authors.initials: JM
authors.lastname: Gao
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liang
authors.forename: Ming-Tang
authors.initials: MT
authors.lastname: Gao
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014815:Vitamins; D002762:Cholecalciferol; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C022616:thiazolyl blue