Antitumor bioactivity of adenovirus-mediated p27mt in colorectal cancer cell line SW480

World J Gastroenterol. 2008 Oct 14;14(38):5827-33. doi: 10.3748/wjg.14.5827.

Abstract

Aim: To explore the antitumor bioactivity of adenovirus-mediated mutant type p27(kip1) gene in a colorectal cancer cell line SW480.

Methods: We constructed recombinant adenovirus vector expressing a mutant type p27(kip1) gene (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), and transduced into SW480 cells. Then we detected expression of p27, Bcl-2 and Bax protein in the transductants by Western blotting, cell cycle of transductants by a digital flow cytometric system, migrating potential with Boyden Chamber and SW480 tumor cell growth inhibition in vitro and in vivo.

Results: We found that a recombinant adenovirus vector of expressing ad-p27mt, with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC) has potent inhibition of SW480 tumor cell growth in vitro and in vivo. Furthermore, ad-p27mt induced cell apoptosis via regulating bax and bcl-2 expressions, and G(1)/S arrest in SW480 cells and inhibited cell migration.

Conclusion: ad-p27mt has a strong anti-tumor bioactivity and has the potential to develop into new therapeutic agents for colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis
  • Base Sequence
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Mutation*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Time Factors
  • Transduction, Genetic
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • CDKN1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cyclin-Dependent Kinase Inhibitor p27