title: Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in metastatic cancer.
abstract: PHII-7, a derivative of indirubin, showed significant anti-cancer activities in vivo and in vitro. We asked whether treating human metastatic cancers and multidrug resistant cancer with PHII-7 would inhibit their invasion and migration. Cell growth was tested by MTT assay and colony formation assay. Apoptosis was examined by flow cytometry. Transwell-based assay and wound healing assay were used to examine cell invasion and migration. Real-time PCR assay and western blot assay were performed to test gene expression on mRNA and protein level, respectively. Firstly, we confirmed that MCF-7/ADR cells showed more invasive and migratory properties compared with MCF-7 cells which were associated with several EMT markers, such as E-cadherin, Slug and vimentin. Secondly, we found that slightly toxic doses of PHII-7 decreased the number of cells that invaded a model epithelial basement membrane and that migrated by switching the molecular signature of the cells from mesenchymal to epithelial. And PHII-7 significantly regulated expression of several epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin, Slug, β-catenin and vimentin. Thirdly, compared with control, PHII-7 inhibited cell proliferation in a time- and dose-dependent manner. Higher doses of PHII-7 also induced apoptosis through activating PARP, caspase-9 and caspase-3. PHII-7 significantly inhibited invasion and migration in both metastatic cancers and multidrug resistant cancer. Our results may provide several data for future application of PHII-7 on drug design and patients treatment.
  
  
  BACKGROUND
  PHII-7, invasion, migration, multidrug resistance, epithelial-mesenchymal transition.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: K X
authors.initials: KX
authors.lastname: Wu
authors.forename: Y H
authors.initials: YH
authors.lastname: Ding
authors.forename: D M
authors.initials: DM
authors.lastname: Fan
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: D S
authors.initials: DS
authors.lastname: Xiong