Dianthin-EGF is an effective tumor targeted toxin in combination with saponins in a xenograft model for colon carcinoma

Future Oncol. 2014 Nov;10(14):2161-75. doi: 10.2217/fon.14.164.

Abstract

Aims: The intention of this work was to lift saponin supported tumor targeted therapies onto the next level by using targeted toxins in nude mice xenotransplant models.

Materials & methods: Combined application of dianthin coupled to EGF and saponin SO-1861 was tested in a xenograft model of colon carcinoma. In vitro cytotoxicity was tested in real-time in NIH3T3 cells (no human EGF receptor expression), HER14 and human colon carcinoma HCT116 (both EGF receptor overexpressing) cells. A xenograft model was established using HCT116 cells and tumor-bearing animals were treated with SO-1861 (30 µg/treatment) and dianthin coupled to EGF (0.35 µg/treatment). Tumor progression was monitored, using (18)F-2-fluor-2-desoxy-d-glucose, by small animal PET and by x-ray computed tomography.

Results: In vitro results demonstrated a high-receptor specificity and the in vivo experiment showed a progressive reduction of the tumor volume and glycolytic activity in the treated group (>95% reduction; p < 0.05).

Conclusion: This therapy has great advantage because of high specificity, low side effects and great effectiveness for future development in the treatment of colon cancer.

Keywords: colon cancer; dianthin-EGF; saponin SO-1861; targeted toxins; targeted tumor therapy; xenograft model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Dianthus / chemistry
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Epidermal Growth Factor
  • Hemolysis / drug effects
  • Humans
  • Immunotoxins / administration & dosage
  • Immunotoxins / adverse effects
  • Immunotoxins / pharmacology*
  • Male
  • Mice
  • Positron-Emission Tomography
  • Ribosome Inactivating Proteins, Type 1
  • Saponins / administration & dosage
  • Saponins / adverse effects
  • Saponins / pharmacology*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Immunotoxins
  • Ribosome Inactivating Proteins, Type 1
  • Saponins
  • Epidermal Growth Factor