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

Insulin-like growth factor binding proteins (IGFBPs) are secreted into the extra-cellular matrix and inhibit cell growth through IGF-dependent and -in dependent 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 lints in vitro with an adenovirus expressing human IGFBP-6 under the control of a CM V promoter (Ad5CMV-BP6) reduced NSCLC cell number through activation of pro grammed cell death, as shown by cell staining with Hoechst 33342 or DIVA en d-labeling with bromodeoxyuridine triphosphate, The growth regulatory effec t of IGFBP-6 was investigated in vivo by intratumoral injection of Ad5CMV-B P6 in NSCLC xenografts established in nu/nu mice. A single injection of Ad5 CMV-BP6 reduced the size of NSCLC xenografts by 45%. These findings indicat e 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 th erapeutics.