Recombinant lentivirus targeting the pleotrophin gene reduces pleotrophin protein expression in pancreatic cancer cells and inhibits neurite outgrowth of dorsal root ganglion neurons

Mol Med Rep. 2014 Mar;9(3):999-1004. doi: 10.3892/mmr.2014.1918. Epub 2014 Jan 24.

Abstract

The objectives of the present study were to construct the recombinant primate lentivirus‑short hairpin RNA-pleiotrophin (pLV-shRNA-PTN) vector, to investigate the silencing effect of pLV-shRNA-PTN on PTN expression in MIA PaCa-2 cells and to observe the inhibition efficiency of pLV-shRNA‑PTN on neurite outgrowth from dorsal root ganglion (DRG) neurons in vitro. The construction procedure for recombinant lentivirus pLV-shRNA-PTN has been described previously. In the present study, pLV-shRNA‑PTN was used to infect MIA PaCa-2 pancreatic cancer cells and the efficiency of the knockdown of the PTN gene on day 7 following infection was analyzed using western blotting. The morphological changes in the cultured DRG neurons were observed by monoculture of DRG neurons and co-culture with MIA PaCa-2 cells in vitro. The recombinant lentivirus pLV-shRNA‑PTN was successfully constructed. The western blot analysis showed that the inhibition rates of PTN expression were 46, 80, 20 and 21%, respectively, following pLV-shRNA‑PTN-A, B, C and D infection. pLV-shRNA-PTN‑B showed the highest knockdown efficiency. DRG neurons co-cultured with infected MIA PaCa-2 cells were decreased in size when compared with the control, and there was a significant decrease in the number and length of neurites. The results suggest that efficient and specific knockdown of PTN in MIA PaCa-2 pancreatic cancer cells and the subsequent reduction in PTN expression results in the inhibition of neurite outgrowth from DRG neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics*
  • Cytokines / metabolism*
  • Ganglia, Spinal / cytology*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Lentivirus / genetics*
  • Mice
  • Neurites / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transduction, Genetic

Substances

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