• Jessica A Yu, David Mauchley, Howard Li, Xianzhong Meng, Raphael A Nemenoff, David A Fullerton, and Michael J Weyant.
• Section of General Thoracic Surgery, Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.
• J. Thorac. Cardiovasc. Surg.. 2012 Nov 1;144(5):1185-91.

ObjectiveGroup IIa secretory phospholipase A2 (sPLA2 IIa) plays a role in the malignant potential of several epithelial cancers. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. We hypothesized that knockdown of sPLA2 in lung cancer cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo.MethodsTwo human non-small cell lung cancer cell lines (A549 and H358) were transduced with short hairpin RNA targeting sPLA2 group IIa. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of sPLA2 IIa messenger RNA and protein, respectively. Cell proliferation was evaluated by the 5-bromo-2'-deoxyuridine DNA labeling assay. NF-κB phosphorylation was assayed by western blot. 1 × 10(6) of A549 or A549 sPLA2 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 23 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for sPLA2 IIa messenger RNA expression.ResultssPLA2 knockdown reduced NF-κB phosphorylation and tumor growth in vivo. A549 wild-type tumors grew twice as fast as knockdown tumors. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. Explanted knockdown tumors maintained lower sPLA2 levels compared with wild-type, confirmed by reverse transcriptase-polymerase chain reaction.ConclusionsKnockdown of sPLA2 IIa suppresses lung cancer growth in part by attenuating NF-κB activity. These findings justify further investigation into the cellular mechanisms of sPLA2 in lung cancer and its potential role as a therapeutic target.Copyright © 2012. Published by Mosby, Inc.

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