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Tuberculosis & Respiratory Diseases

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Vol.58 No.2
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Synergism Induced by Combination of Farnesyl Transferase Inhibitor SCH66336 and Insulin like-Growth Factor Binding Protein-3 in poptosis of Non-Small Cell Lung Cancer Cell lines

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2005, v.58 no.2, pp.120-128







& (2005). Synergism Induced by Combination of Farnesyl Transferase Inhibitor SCH66336 and Insulin like-Growth Factor Binding Protein-3 in poptosis of Non-Small Cell Lung Cancer Cell lines. Tuberculosis & Respiratory Diseases, 58(2), 120-128.
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Abstract

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.(Tuberc Respir Dis 2005; 58:120-128)

keywords
Non-small cell lung cancer, Insulin-like growth factor binding protein-3, Farnesyl transferase inhibitor

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