Journal
FUTURE ONCOLOGY
Volume 10, Issue 14, Pages 2161-2175Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fon.14.164
Keywords
colon cancer; dianthin-EGF; saponin SO-1861; targeted toxins; targeted tumor therapy; xenograft model
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Funding
- Deutsche Forschungsgemeinschaft [TH 1810/1-1, WE 4784/1-1]
- Wilhelm Sander-Stiftung [2011.121.1]
- Stiftung der Deutschen Wirtschaft
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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 mu g/treatment) and dianthin coupled to EGF (0.35 mu g/treatment). Tumor progression was monitored, using F-18-2-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.
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