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Synergism Induced by Combination of Farnesyl Transferase Inhibitor SCH66336 and Insulin like-Growth Factor Binding Protein-3 in apoptosis of Non-Small Cell Lung Cancer Cell lines  

Kim, Young (Department of Internal Medicine, Yonsei University College of Medicine)
Kim, Se Kyu (Department of Internal Medicine, Yonsei University College of Medicine)
Kim, Hyung Jung (Department of Internal Medicine, Yonsei University College of Medicine)
Chang, Joon (Department of Internal Medicine, Yonsei University College of Medicine)
Ahn, Chul Min (Department of Internal Medicine, Yonsei University College of Medicine)
Kim, Sung Kyu (Department of Internal Medicine, Yonsei University College of Medicine)
Chang, Yoon Soo (Department of Internal Medicine, Yonsei University College of Medicine)
Publication Information
Tuberculosis and Respiratory Diseases / v.58, no.2, 2005 , pp. 120-128 More about this Journal
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.
Keywords
Non-small cell lung cancer; Insulin-like growth factor binding protein-3; Farnesyl transferase inhibitor;
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