Enhanced anti-tumor activity by the combination of TRAIL/Apo-2L and combretastatin A-4 against human colon cancer cells via induction of apoptosis in vitro and in vivo

Cancer Lett. 2011 Mar 1;302(1):11-9. doi: 10.1016/j.canlet.2010.12.001. Epub 2011 Jan 14.

Abstract

The present study indicated that the combination of TRAIL/Apo-2L and CA-4 exerted synergistic anti-proliferative effect against human colon carcinoma cells including SW-620 and HCT-116 in vitro. Moreover, the increased anti-tumor efficacy of TRAIL/Apo-2L combined with CA-4 was further validated on SW-620 xenograft model in nude mice. These enhanced anti-cancer activities were accompanied by caspase-mediated apoptosis. Furthermore, it was identified that NF-κB as the major determinant of TRAIL/Apo-2L resistance could be blocked in cytoplasm by TRAIL/Apo-2L plus CA-4 treatment. Taken together, these findings build the rationale for further (pre)clinical development of TRAIL/Apo-2L and CA-4 against colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • HCT116 Cells
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Transport / drug effects
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • NF-kappa B
  • Stilbenes
  • TNF-Related Apoptosis-Inducing Ligand
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • fosbretabulin