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Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

2000; Springer Nature; Volume: 19; Issue: 38 Linguagem: Inglês

10.1038/sj.onc.1203813

1476-5594

Naoko Sueoka, Ho‐Young Lee, Sandra Wiehle, Richard J. Cristiano, BingLiang Fang, Lin Ji, Jack A. Roth, Waun Ki Hong, Pinchas Cohen, Jonathan M. Kurie,

Cancer, Hypoxia, and Metabolism

Insulin-like growth factor binding proteins (IGFBPs) are secreted into the extra-cellular matrix and inhibit cell growth through IGF-dependent and -independent mechanisms. In this study, we investigated the role of IGFBP-6, a relatively unexplored member of the IGFBP family, in the proliferation of non-small cell lung cancer (NSCLC) cells. Infection of NSCLC cell lines in vitro with an adenovirus expressing human IGFBP-6 under the control of a CMV promoter (Ad5CMV-BP6) reduced NSCLC cell number through activation of programmed cell death, as shown by cell staining with Hoechst 33342 or DNA end-labeling with bromodeoxyuridine triphosphate. The growth regulatory effect of IGFBP-6 was investigated in vivo by intratumoral injection of Ad5CMV-BP6 in NSCLC xenografts established in nu/nu mice. A single injection of Ad5CMV-BP6 reduced the size of NSCLC xenografts by 45%. These findings indicate that IGFBP-6 is a potent inducer of programmed cell death in cancer cells and support investigations into IGFBP-6 as a potential target in cancer therapeutics.