Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer

Cancer Res. 2003 Nov 15;63(22):7724-32.

Abstract

Survivin plays an important role in cancer development. We aim to show here that suppression of survivin expression or function by antisense and dominant-negative (DN) mutant can inhibit gastric cancer carcinogenesis and angiogenesis in vivo. Plasmid constructs expressing survivin antisense and DN mutant replacing the cysteine residue at amino acid 84 with alanine (Cys84Ala) were prepared and introduced into BCG-823 and MKN-45 gastric cancer cells to establish stable transfectants. We showed that both antisense and DN mutant stable transfectants exhibited abnormal morphology, with decreased cell growth and increased rate of spontaneous apoptosis and mitotic catastrophe. Furthermore, in nude mice xenografts, these cells exhibited decreased de novo gastric tumor formation and reduced development of angiogenesis. Results from these studies strongly suggest that survivin is a promising target for gastric cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Animals
  • Apoptosis / genetics
  • Cell Division / genetics
  • Cell Line, Tumor
  • DNA, Antisense / genetics*
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics*
  • Neoplasm Proteins
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy*
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Survivin
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • BIRC5 protein, human
  • DNA, Antisense
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin