title: Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.
abstract: OBJECTIVE
  ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect.
  
  
  METHODS
  Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed.
  
  
  RESULTS
  ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group.
  
  
  CONCLUSIONS
  Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Du
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Chemistry, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Chemistry, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing, China. cpuxianghua@sina.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Nanjing Medical University Affiliated to Nanjing Brain Hospital, No. 264 Guangzhou Road, Nanjing, China. xhnkyy123@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C000606527:3,9-dihydroxy-6-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5H-indeno(1,2-c)isoquinoline-5,11(6H)-dione; D020533:Angiogenesis Inhibitors; D007192:Indenes; D007546:Isoquinolines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Antitumor; Breast cancer; ER520; Ishikawa; MCF-7