Dendritic cells with CED-3 and CED-4 siRNA is effective in prolonging DC lifetime and suppresses tumor growth in gastric cancer

Hepatogastroenterology. 2013 Mar-Apr;60(122):372-6. doi: 10.5754/hge12626.

Abstract

Background/aims: We investigated effects of CED-3 and CED-4-siRNA on prolonging dendritic cell life in vivo and in vitro.

Methodology: The DCs were divided into three groups: pure-DC, siRNA and CED-3 and CED-4-siRNA. we performed anti-apoptosis assays for DCs with flow cytometry. The assay for cytotoxicity assay was performed in vitro by a standard chromium assay at various effector/target ratios. Percent-specific lysis was calculated. We injected three kinds of DCs from tail vein every 3 days, we calculated tumor volume control rate and tumor weight control rate with formula.

Results: The DC percentages of apoptosis of CED-3 and CED-4 siRNA group were (12.09±1.14)%. Tumor-specific CTL activity showed 82.1% specific lysis for CED-3 and CED-4-siRNA DC group and 39.4% and 40.2% specific lysis for pure DC and siRNA DC group respectively. The lysis of CED-3 and CED-4-siRNA group was higher than the any other groups (p<0.05).The experiment of transplantation tumor in BALB/C mice showed that CED-3 and CED-4-siRNA DC can inhibit mice with tumors in volume and weight.

Conclusions: We found that vaccination with CED-3 and CED-4-siRNA was capable of prolonging the survival of antigen-expressing DCs, and generated a strong therapeutic effect in the treatment of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / antagonists & inhibitors*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology
  • Apoptosis*
  • Calcium-Binding Proteins / antagonists & inhibitors*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology
  • Caspases / physiology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA, Small Interfering / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Apoptosis Regulatory Proteins
  • CASP8AP2 protein, human
  • Calcium-Binding Proteins
  • RNA, Small Interfering
  • Caspases