title: SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression.
abstract: BACKGROUND
  The multiple tyrosine kinase inhibitors SU6668 have a promising therapeutic effect on the progression of hematological malignancies and some solid tumors. Here, we determined its effect on triple negative breast cancer (TNBC) cells and explored the potential molecular mechanism.
  
  
  METHODS
  In this study, MDA-MB-231 cells were treated with SU6668 (15 μM, 30 μM) for 72 h and the change of proliferation was examined by MTT and tablet cloning. DNA ploidy was detected by flow cytometric analysis with PI staining. Double-label immunofluorescence method was used to detect the expression and distribution of MTDH proteins. VEGFR2, HIF-1α, MTDH, E-cadhrein, and SMA expressions were detected by Western bolt assay.
  
  
  RESULTS
  This study showed that SU6668 inhibited the proliferation and induced polyploidization of MDA-MB-231 cells in a dose dependent form. SU6668 exposure increased the distribution of MTDH in cytoplasm and decreased its distribution in nuclei. After the treatment of SU6668, VEGFR2, HIF-1α, MTDH and SMA proteins were down-regulated, while E-cadhrein was up-regulated in MDA-MB-231 cells.
  
  
  CONCLUSIONS
  In conclusion, SU6668 exposure maybe induces polyploidization, inhibit EMT and influence the expression of MTDH, which suppresses the proliferation in TNBC cells. MTDH is a key signal protein in downstream of VEGF/HIF-1αpathway in MDA-MB-231 cells, which may be used as the potential target in the treatment of TNBC.
authors.affiliation: Oncology Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Oncology Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Zhaozhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Medical Experimental Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Dongchu
authors.initials: D
authors.lastname: Ma
authors.affiliation: Oncology Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Oncology Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Research of People's Liberation Army, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
authors.affiliation: Oncology Department, Cancer Treatment Center, General Hospital of Shenyang Military Region, Shenyang, P. R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xie