title: Vitamin D3 enhances antitumor activity of metformin in human bladder carcinoma SW-780 cells.
abstract: OBJECTIVE
  To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism.
  
  
  METHODS
  MTT assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K, p-S6.
  
  
  RESULTS
  MTT results showed that 320 μg/ml vitamin D3 combined with 620 μg/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased.
  
  
  CONCLUSIONS
  Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.
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; 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; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014815:Vitamins; D002762:Cholecalciferol; D008687:Metformin; D058570:TOR Serine-Threonine Kinases; C022616:thiazolyl blue