title: Antiangiogenic activities and cisplatin-combined antitumor activities of BPR0L075.
abstract: BACKGROUND
  Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4.
  
  
  METHODS
  In vitro/in vivo models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude mice, and murine leukemia cells-inoculated mice were utilized to evaluate BPR0L075 for antiangiogenic and antitumoral activity spectra.
  
  
  RESULTS
  BPR0L075 concentration-dependently inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs), disrupted capillary tube formations of HUVECs and rat aorta endothelial cells, and suppressed in vivo VEGF-mediated angiogenesis in Matrigel plugs in mice. Besides inhibiting the colony growth of cancer cells, BPR0L075 suppressed growth of subcutaneously-xenografted human lung, colorectal, and cervical solid tumors in nude mice. Combination treatments of BPR0L075 plus cisplatin, compared to either agent alone, demonstrated a stronger growth inhibition against the tumor xenografts in nude mice and longer lifespan in the leukemia mice.
  
  
  CONCLUSIONS
  BPR0L075 is an antitumoral and antiangiogenic agent and potentiates the anticancer activity of cisplatin.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan, R.O.C.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Chih-Bo
authors.initials: CB
authors.lastname: Hu
authors.forename: Kai-Chia
authors.initials: KC
authors.lastname: Yeh
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Fei-Feng
authors.initials: FF
authors.lastname: Tung
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hwang
authors.forename: Huan-Yi
authors.initials: HY
authors.lastname: Tseng
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Huang
authors.forename: Horng-Shing
authors.initials: HS
authors.lastname: Shy
authors.forename: Su-Huei
authors.initials: SH
authors.lastname: Hsieh
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Shen
authors.forename: Hsin-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
chemical_list: C488735:6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole; D020533:Angiogenesis Inhibitors; D007211:Indoles; D002945:Cisplatin