PAd-shRNA-PTN reduces pleiotrophin of pancreatic cancer cells and inhibits neurite outgrowth of DRG

World J Gastroenterol. 2011 Jun 7;17(21):2667-73. doi: 10.3748/wjg.v17.i21.2667.

Abstract

Aim: To investigate the silencing effects of pAd-shRNA-pleiotrophin (PTN) on PTN in pancreatic cancer cells, and to observe the inhibition of pAd-shRNA-PTN on neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro.

Methods: PAd-shRNA-PTN was used to infect pancreatic cancer BxPC-3 cells; assays were conducted for knockdown of the PTN gene on the 0th, 1st, 3rd, 5th, 7th and 9th d after infection using immunocytochemistry, real-time quantitative polymerase chain reaction (PCR), and Western blotting analysis. The morphologic changes of cultured DRG neurons were observed by mono-culture of DRG neurons and co-culture with BXPC-3 cells in vitro.

Results: The real-time quantitative PCR showed that the inhibition rates of PTN mRNA expression in the BxPC-3 cells were 20%, 80%, 50% and 25% on the 1st, 3rd, 5th and 7th d after infection. Immunocytochemistry and Western blotting analysis also revealed the same tendency. In contrast to the control, the DRG neurons co-cultured with the infected BxPC-3 cells shrunk; the number and length of neurites were significantly decreased.

Conclusion: Efficient and specific knockdown of PTN in pancreatic cancer cells and the reduction in PTN expression resulted in the inhibition of neurite outgrowth from DRG neurons.

Keywords: Dorsal root ganglion; Neurite outgrowth; Pancreatic cancer; Pleiotrophin; RNA interference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics*
  • Cytokines / metabolism*
  • Ganglia, Spinal / cytology*
  • Neurites / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*

Substances

  • Carrier Proteins
  • Cytokines
  • RNA, Small Interfering
  • pleiotrophin