Stable knockdown of Aurora-A by vector-based RNA interference in human esophageal squamous cell carcinoma cell line inhibits tumor cell proliferation, invasion and enhances apoptosis

Cancer Biol Ther. 2009 Oct;8(19):1852-9. doi: 10.4161/cbt.8.19.9550.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers, and the existing treatment approaches have not been able to effectively manage this dreaded cancer. Therefore, continuing efforts are ongoing to explore novel targets and strategies for the management of ESCC. It has been shown that amplification and overexpression of the Aurora-A occur in several types of human tumors, including ESCC. Moreover, overexpression of Aurora-A is shown to associate with the grades of tumor differentiation and metastasis of ESCC. These render Aurora-A an interesting target for antitumor therapy. Recently, vector-based RNA interference (RNAi) expression systems have been successfully used to silence gene expression, but knockdown of Aurora-A by vector-based RNAi as a therapeutic model for ESCC treatment is not fully established. In this study, we used a DNA vector-based RNAi approach by expressing short hairpin RNA (shRNA) to knockdown Aurora-A. Western blotting analysis and reverse transcription PCR (RT-PCR) showed that expressions of Aurora-A were efficiently downregulated at both the protein and mRNA levels by stable transfection with Aurora-A siRNA expression vector. The stable suppression of Aurora-A expression inhibited the proliferation and invasion of EC9706 cells. Furthermore, when Aurora-A was stably downregulated, cisplatin-induced cytotoxic effects and apoptosis were increased dramatically. These data indicate that vector-mediated silencing of the Aurora-A gene may provide new avenues toward the study of the role of Aurora-A overexpression in tumor cells. Make a novel therapeutic approach to treatment of ESCC and other malignant tumors overexpressing Aurora-A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Aurora Kinases
  • Blotting, Western
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Gene Knockdown Techniques / methods*
  • Humans
  • Neoplasms, Squamous Cell / enzymology
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / pathology
  • Neoplasms, Squamous Cell / therapy*
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / deficiency*
  • Protein-Serine-Threonine Kinases / genetics
  • RNA Interference
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • RNA, Small Interfering
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases