Wnt inhibitory factor inhibits lung cancer cell growth.
OBJECTIVE
Aberrant activation of the Wnt signaling pathway is associated with the pathogenesis of multiple cancers, including non-small cell lung cancer. Wnt inhibitory factor, a secreted Wnt antagonist, is downregulated in non-small cell lung cancer. We hypothesized that restoration of Wnt inhibitory factor function would inhibit lung cancer cell growth.


METHODS
The lung cancer cell lines A549 and H460 were transfected with an expression vector containing the Wnt inhibitory factor gene. Apoptosis rates and colony formation were measured after transfection. Recombinant Wnt inhibitory factor protein was used to treat H460 cells, and proliferation rates were measured with an MTS assay. Finally, Wnt inhibitory factor plasmid was peritumorally injected near H460 tumor xenografts in nude mice.


RESULTS
Wnt inhibitory factor-transfected cells had increased apoptosis and decreased colony formation than control cells. Recombinant human Wnt inhibitory factor protein was also able to inhibit H460 cell proliferation measured by using the MTS assay. Wnt inhibitory factor plasmid significantly inhibited the growth in vivo of H460 tumor xenografts in nude mice.


CONCLUSIONS
These data suggest that Wnt inhibitory factor is able to inhibit lung cancer cell growth both in vitro and in vivo and provides additional evidence that Wnt inhibitory factor plays an important role in Wnt pathway regulation in lung cancer.
Kim
Jae
J
Thoracic Oncology Laboratory, UCSF Comprehensive Cancer Center, San Francisco, Calif 94143, USA.
You
Liang
L
Xu
Zhidong
Z
Kuchenbecker
Kris
K
Raz
Dan
D
He
Biao
B
Jablons
David
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014162:Transfection; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000494:pharmacology*
D051153:Wnt Proteins