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 -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.
Sueoka
N
N
Department of Thoracic/Head and Neck Medical Oncology, University of Texas-MD Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Lee
H Y
HY
Wiehle
S
S
Cristiano
R J
RJ
Fang
B
B
Ji
L
L
Roth
J A
JA
Hong
W K
WK
Cohen
P
P
Kurie
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015197:Carcinogenicity Tests; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002455:Cell Division; D053938:DNA Fragmentation; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018976:Insulin-Like Growth Factor Binding Protein 6