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J Thorac Cardiovasc Surg 2007;133:733-737
© 2007 The American Association for Thoracic Surgery

General Thoracic Surgery

Wnt inhibitory factor inhibits lung cancer cell growth

Jae Kim, MD, Liang You, MD, PhD, Zhidong Xu, PhD, Kris Kuchenbecker, BS, Dan Raz, MD, Biao He, PhD, David Jablons, MD*

Thoracic Oncology Laboratory, UCSF Comprehensive Cancer Center, San Francisco, Calif.

Read at the Eighty-sixth Annual Meeting of The American Association for Thoracic Surgery, Philadelphia, Pa, April 29-May 3, 2006.

Received for publication May 22, 2006; revisions received September 15, 2006; accepted for publication September 29, 2006.

* Address for reprints: David Jablons, MD, Box 1724, 2200 Post St, Mount Zion Building C, University of California, San Francisco, San Francisco, CA 94143. (Email: jablonsd{at}surgery.ucsf.edu).

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.

Conclusion: 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.

Abbreviations and Acronyms RT-PCR = reverse transcription–polymerase chain reaction; WIF-1 = Wnt inhibitory factor


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