N. Sueoka et al., Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells, ONCOGENE, 19(38), 2000, pp. 4432-4436
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.