A vector-based short hairpin RNA targeting Aurora A inhibits breast cancer growth

Int J Oncol. 2010 May;36(5):1121-8.

Abstract

Aurora A plays an essential role in centrosome maturation, separation and in the formation of the mitotic bipolar spindle. Overexpression or amplication of Aurora A gene has been detected in many cancer cell lines and various tumor tissues, including breast cancer, suggesting that Aurora A might be drug target for breast cancer treatment. In the current study, short hairpin RNA targeting Aurora A was cloned into pGenesil-2 plasmid vector and then transfected into MDA-MB-435S and ZR-75-30 human breast cancer cells using cationic liposome. Reduced expression of Aurora A was detected by RT-PCR and Western blot. The effect of pGenesil-2-shAURKA plasmid on tumor growth in MDA-MB-435S xenogenic implantation model was studied. pGenesil-2-shAURKA plasmid inhibited tumor growth significantly by systemantic administration. To further study the underlying mechanisms, cell apoptosis and proliferation were investigated by flow cytometric analysis, propidium iodide staining, TUNEL and Ki-67 immunostaining respectively. Increased apoptosis and reduced cell proliferation were detected in vitro and in vivo studies. In summary, our results suggested that specific knockdown of Aurora A expression by vector based shRNA may be a potential therapy for human breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cations
  • Cell Line, Tumor
  • DNA / metabolism*
  • Female
  • Flow Cytometry / methods
  • Genetic Techniques
  • Genetic Vectors*
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Liposomes / chemistry
  • Neoplasm Transplantation
  • Protein Serine-Threonine Kinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cations
  • Ki-67 Antigen
  • Liposomes
  • DNA
  • Aurora Kinases
  • Protein Serine-Threonine Kinases