title: Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down-regulate Akt and MMP-2.
abstract: OBJECTIVE
  As prognosis for patients with metastatic ovarian cancer is generally poor, advances in treatment are needed. Here, we studied the mechanism of action of a recombinant viral capsid protein (rVP1) and explored its effect against ovarian tumour growth and metastasis in vivo.
  
  
  METHODS
  The human ovarian cancer cell line SKOV3 and BALB/cAnN-Foxn1 female nude mice were used. Effects of rVP1 on the viability, invasive ability, matrix metalloproteinase (MMP)-2 activity and cancer cell proliferation and metastasis were determined by cell proliferation assay, Matrigel invasion assay, gelatin zymographic analysis, as well as bioluminescence imaging and immunohistological analysis in xenograft mouse models respectively. Levels of total and phosphorylated focal adhesion kinase (FAK), PKB/Akt, phosphatase and tensin homologue (PTEN) and glycogen synthase kinase-3β (GSK-3β) were detected by Western blotting.
  
  
  RESULTS
  rVP1 promoted apoptosis and decreased invasion of human ovarian cancer cells. This effect of rVP1 was accompanied by activation of PTEN and GSK-3β as well as down-regulation of FAK, Akt and MMP-2. Anti-integrin antibodies or overexpression of constitutively active Akt reversed the cellular effects of rVP1. Orthotopic and intraperitoneal xenograft mouse models demonstrated that rVP1 attenuated survival and metastasis of human ovarian cancer SKOV3 cell line in vivo through selective regulation of Akt and GSK-3β activity as shown by bioluminescence imaging of mice and immunohistochemical analysis.
  
  
  CONCLUSIONS
  These results indicate that negative regulation of Akt signalling and MMP-2 by rVP1 may have the potential to suppress ovarian tumour growth and metastasis in vivo.
authors: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors: Jei-Ming
authors: JM
authors: Peng
authors: Yee-Hsiung
authors: YH
authors: Chen
authors: Shao-Wen
authors: SW
authors: Hung
authors: Ching-Feng
authors: CF
authors: Chiu
authors: Ming-Yi
authors: MY
authors: Ho
authors: Yi-Jen
authors: YJ
authors: Lee
authors: Tsung-Ching
authors: TC
authors: Lai
authors: Michael
authors: M
authors: Hsiao
authors: Chi-Ming
authors: CM
authors: Liang
authors: Shu-Mei
authors: SM
authors: Liang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D036022:Capsid Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D036022:Capsid Proteins; D039081:Integrin alpha5beta1; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2