title: [Inhibitory effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1].
abstract: OBJECTIVE
  To explore the in vitro anti-tumor effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1.
  
  
  METHODS
  The cytotoxic effects of zoledronic acid on HNE1 cells were detected by MTT assay, invasion of HNE1 cells by Transwell assay, secretion of (vascular endothelial growth factor)VEGF by (enzyme-linked immunosorbent assay) ELISA and the activities of MMP (matrix metalloproteinase) 2 and MMP9 by gelatine zymography. And the expressions of mRNA and proteins of MMP2, MMP9 and VEGF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.
  
  
  RESULTS
  After a treatment of zoledronic acid at 2.5, 5, 10, 20 and 40 mol/L for 48 h or 72 h, the highest inhibition rate of proliferation at approximately 50% was observed in the 40 mol/L group after 72 h. The inhibitory effect was not in a dose/time-dependent manner. After a 24-hour treatment of zoledronic acid at different concentrations (0, 10, 20 and 40 mol/L), the numbers of membrane-invading cells were 75.8 ± 2.6, 54.8 ± 5.4, 44.6 ± 6.4 and 38.6 ± 8.2 respectively (all P < 0.01). Gelatinase zymography demonstrated that the activities of MMP2 and MMP9 were inhibited significantly only in cells treated at 0 µmol/L. After a 24-hour exposure to zoledronic acid at 0, 10, 20 and 40 µmol/L, the concentrations of VEGF in supernatant were (5264 ± 89), (4626 ± 30), (4155 ± 40) and (1908 ± 171) g/L respectively (all P < 0.01). The expressions of mRNA and protein of MMP2, MMP9 and VEGF were down-regulated.
  
  
  CONCLUSIONS
  Zoledronic acid can inhibit the in vitro proliferation and invasion of HNE1 cell through suppressing the secretion of VEGF, the activities of MMP2 and MMP9 and the expressions of VEGF, MMP2 and MMP9.
authors.affiliation: Department of Medical Oncology, Shantou University Medical College, Shantou, China.
authors.forename: Xu-yuan
authors.initials: XY
authors.lastname: Li
authors.forename: Ying-cheng
authors.initials: YC
authors.lastname: Lin
authors.forename: Wan-lan
authors.initials: WL
authors.lastname: Huang
authors.forename: Hong-biao
authors.initials: HB
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Lin
authors.forename: Chao-qun
authors.initials: CQ
authors.lastname: Hong
authors.forename: Jiong-yu
authors.initials: JY
authors.lastname: Chen
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077211:Zoledronic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9