| Autor: |
Seifalian Alexander M, Fuller Barry J, Sales Kevin M, Yang Shi Yu, Winslet Marc C |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
|
| Zdroj: |
Molecular Cancer, Vol 7, Iss 1, p 17 (2008) |
| Druh dokumentu: |
article |
| ISSN: |
1476-4598 |
| DOI: |
10.1186/1476-4598-7-17 |
| Popis: |
Abstract Background The resistance of tumour cells to apoptosis is a major contributor to the limited effectiveness of chemotherapies. Insulin-like growth factor I (IGF-I) has potential to protect cancer cells from variety of apoptotic challenges. This study was carried out to investigate the effect of a novel IGF-I receptor antagonist on apoptosis in colon cancer cells. Results We have designed and synthesised a novel antagonist of IGF-I receptor. The effect of this antagonist on human colon cancer cell proliferation was examined by a non-radioactive assay; the apoptosis was revealed by determining the activities of cellular caspases3/7, 8 and 9. The apoptosis pathways were investigated by examining the levels of pro-apoptosis proteins with Western blotting. Following 40 hours treatment with the novel antagonist peptide, colon cancer cell Caspase 3/7 activities increased 2–7 times; Caspase 8 activities increased 2–5 times and Caspase 9 increased 1.2–1.6 times. The proliferation of cancer cell was inhibited by 14–15%. The data showed that the antagonist induced colon cancer cell apoptosis and inhibited cancer cell proliferation. The different changes of Caspase 3/7, 8 and 9 activities suggested that the extrinsic pathways may play a major role in the antagonist peptide-induced apoptosis. Conclusion This is the first report on this novel antagonist to induce human colon cancer cell apoptosis and inhibit cancer cell proliferation. These results suggest that IGF-I receptor antagonists may have the potential to be developed as a novel therapy for colon cancers in the future. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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