siRNA targeting of Cdx2 inhibits growth of human gastric cancer MGC-803 cells

World J Gastroenterol. 2012 Apr 28;18(16):1903-14. doi: 10.3748/wjg.v18.i16.1903.

Abstract

Aim: To investigate the effects of small interference RNA (siRNA) targeting of Cdx2 on human gastric cancer MGC-803 cells in vitro and in vivo.

Methods: The recombinant pSilencer 4.1-Cdx2 siRNA plasmids were constructed and transfected into gastric cancer MGC-803 cells in vitro. The stable transfectants were selected. The effects of Cdx2 siRNA on growth, proliferation, cell cycle, apoptosis, migration and invasiveness of human gastric cancer MGC-803 cells were evaluated and the expression of phosphatase and tensin homolog (PTEN), caspase-9 and caspase-3 was observed in vitro by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting analysis. We also investigated the effect of Cdx2 siRNA on growth of MGC-803 cells in nude mice in vivo.

Results: Cdx2 siRNA led to inhibition of endogenous Cdx2 mRNA and protein expression as determined by RT-PCR and Western blotting analysis. Cdx2 siRNA significantly inhibited cell growth and proliferation, blocked entry into the S-phase of the cell cycle, induced cell apoptosis, and reduced the motility and invasion of MGC-803 cells. Cdx2 siRNA also increased PTEN expression, and activated caspase-9 and caspase-3 in MGC-803 cells in vitro . In addition, siRNA targeting of Cdx2 inhibited the growth of MGC-803 cells and promoted tumor cell apoptosis in vivo in nude mice tumor models.

Conclusion: Cdx2 was involved in regulating pro-gression of human gastric cancer cells MGC-803. Manipulation of Cdx2 expression may be a potential therapeutic strategy for gastric cancer.

Keywords: Cdx2; Gastric cancer; Growth; Small interference RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDX2 Transcription Factor
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / physiology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / analysis
  • RNA, Messenger / analysis
  • RNA, Small Interfering / genetics*
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / therapy
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / physiology*

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Cdx2 protein, mouse
  • Homeodomain Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • PTEN Phosphohydrolase
  • Caspase 3
  • Caspase 9