TY - JOUR
T1 - Prolonged exposure of colon cancer cell to the epidermal growth factor receptor inhibitor gefitinib (Iressa™) and to the antiangiogenic agent ZD6474
T2 - Cytotoxic and biomolecular effects
AU - Azzariti, Amilia
AU - Porcelli, Letizia
AU - Xu, Jian Ming
AU - Simone, Grazia Maria
AU - Paradiso, Angelo
PY - 2006/8/28
Y1 - 2006/8/28
N2 - Aim: To analyze the biological effects of prolonged in Vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib (Iressal™), an inhibitor of epidermal growth factor receptor (EGFR) activity, and ZD6474, an inhibitor of both KDR and EGFR activities. Methods: Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent (4 d of drug exposure followed by 3 d of washout each week) schedule. Results: In both cell types, prolonged exposure (up to 14 d) to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erkl/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. Conclusion: We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.
AB - Aim: To analyze the biological effects of prolonged in Vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib (Iressal™), an inhibitor of epidermal growth factor receptor (EGFR) activity, and ZD6474, an inhibitor of both KDR and EGFR activities. Methods: Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent (4 d of drug exposure followed by 3 d of washout each week) schedule. Results: In both cell types, prolonged exposure (up to 14 d) to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erkl/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. Conclusion: We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.
KW - Chemo-resistance
KW - Colon cancer
KW - Gefitinib
KW - Tyrosine kinase
KW - ZD6474
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M3 - Article
C2 - 16937523
AN - SCOPUS:33748490710
VL - 12
SP - 5140
EP - 5147
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 32
ER -