Newcastle disease virus induces apoptosis in cisplatin-resistant human lung adenocarcinoma A549 cells in vitro and in vivo

Cancer Lett. 2012 Apr 1;317(1):56-64. doi: 10.1016/j.canlet.2011.11.008. Epub 2011 Nov 15.

Abstract

Cisplatin (DDP) is widely used in lung cancer chemotherapy. However, cisplatin resistance represents a major obstacle in effective clinical treatment. This study aims to investigate whether Newcastle disease virus (NDV) exhibits an oncolytic effect on cisplatin-resistant A549 lung cancer cells. We found that NDV induced A549/DDP cell apoptosis via the caspase pathway, particularly involving caspase-9, while the mitogen-activated protein kinase (MAPK) and Akt pathways also contributed to apoptotic induction. Furthermore, NDV displayed oncolytic effects in a mouse A549/DDP lung cancer model. Collectively, our data indicate that NDV could overcome the cisplatin resistance in lung cancer cells in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adenocarcinoma / virology
  • Adenocarcinoma of Lung
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lung Neoplasms / virology
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • Newcastle disease virus / growth & development
  • Newcastle disease virus / pathogenicity*
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / growth & development
  • Oncolytic Viruses / pathogenicity*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Time Factors
  • Virus Replication
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • CASP9 protein, human
  • Caspase 9
  • Cisplatin