Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma

Oncol Rep. 2011 Apr;25(4):989-95. doi: 10.3892/or.2011.1149. Epub 2011 Jan 18.

Abstract

Expression levels of the novel tumor suppressor gene REIC/Dkk-3 are reduced in many human cancers. We have previously showed that an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) induced apoptosis of cancer cells selectively and exerted bystander antitumor effects via ER stress. We examined possible effects of Ad-REIC in a peritoneal dissemination model of scirrhous gastric carcinoma (SGC). Among various types of gastric cancer, SGC continues to be associated with the worst prognosis due to a high incidence of metastases in the peritoneal cavity. We found that a single intraperitoneal injection of Ad-REIC suppressed tumor dissemination and disease progression. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that Ad-REIC gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma, Scirrhous / genetics
  • Adenocarcinoma, Scirrhous / pathology
  • Adenocarcinoma, Scirrhous / therapy*
  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Line, Tumor
  • Chemokines
  • Female
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage*
  • Humans
  • Immunoenzyme Techniques
  • Injections, Intraperitoneal
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokines
  • DKK3 protein, human
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger