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. 2001 Dec;85(12):2017–2021. doi: 10.1054/bjoc.2001.2171

Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells

B Wen 1,#, E Deutsch 1,#, E Marangoni 1, V Frascona 1, L Maggiorella 1, B Abdulkarim 1, N Chavaudra 1, J Bourhis 1
PMCID: PMC2364012  PMID: 11747348

Abstract

Insulin-like growth factor-1 (IGF-1) plays an important growth-promoting effect by activating the PI3K/Akt signalling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. Tyrphostin AG 1024, one selective inhibitor of IGF-1R, was used to evaluate effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to Tyrphostin AG 1024 inhibited proliferation and induced apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) was up to 50% compared to the control. Examination of Tyrphostin AG 1024 effects on radiation response demonstrated a marked enhancement in radiosensitivity and amplification of radiation-induced apoptosis. Western blot analysis indicated that Tyrphostin AG 1024-induced apoptosis was associated with a downregulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression, especially when combined with irradiation. To our knowledge, this is the first report showing that an IGF-1 inhibitor was able to markedly increase the response of tumour cells to ionizing radiation. These results suggest that Tyrphostin AG 1024 could be used as a potential therapeutic agent in combination with irradiation.   http://www.bjcancer.com © 2001 Cancer Research Campaign

Keywords: IGF-1R inhibitor, apoptosis, radiosensitivity, breast cancer

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Selected References

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