title: Targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis of osteosarcoma cells in vitro.
abstract: OBJECTIVE
  To investigate the effect of targeted antiosteosarcoma methotrexate-bisphosphonate conjugate on growth inhibition and apoptosis in human osteosarcoma MG-63 cells.
  
  
  METHODS
  MG-63 cells were treated with various concentrations of methotrexate-bisphosphonate conjugate and apoptosis was monitored via an MTT assay, cell morphology, TUNEL assay and flow cytometry analysis.
  
  
  RESULTS
  The survival rate of MG-63 cells treated for 24 to 96 hours with 2000 mg/ml or more of methotrexate-bisphosphonate conjugate decreased significantly. Cells treated with conjugate showed typical apoptotic features using inverted phase contrast microscopy and fluorescence staining, and the majority of cells demonstrated a positive result in the TUNEL assay. Karyopyknosis and crescent aggregation of chromatin were observed in conjugate-treated cells by electron microscopy. Flow cytometry of MG-63 cells treated with methotrexate-bisphosphonate conjugate showed a time and dose-dependent increase in apoptosis (p < 0.05).
  
  
  CONCLUSIONS
  A targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis in human osteosarcoma MG-63 cells. This new conjugate is a valuable experimental tool for the therapy of osteosarcoma.
authors: Orthopedic Department, Xuzhou No. 1 Hospital, Xuzhou, China. tomzeng5@163.com.
authors: X-N
authors: XN
authors: Yang
authors: J-C
authors: JC
authors: Zeng
authors: Y-C
authors: YC
authors: Song
authors: H
authors: H
authors: Zhang
authors: F-X
authors: FX
authors: Pei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D004164:Diphosphonates; C097566:methotrexate bisphosphonate; D008727:Methotrexate