A Synthetic CPP33-Conjugated Active Domain Peptide Inhibits Invasion Ability of Non-Small Lung Cancer Cells.

Homeobox A9 () expression is associated with the aggressive growth of cancer cells and poor prognosis in lung cancer. Previously, we showed that can serve as a potential therapeutic target for the treatment of metastatic non-small cell lung cancer (NSCLC). In the present study, we have carried out additional studies toward the development of a peptide-based therapeutic agent. Vectors expressing partial DNA fragments of were used to identify a unique domain involved in the inhibition of NSCLC cell invasion. Next, we performed in vitro invasion assays and examined the expression of EMT-related genes in transfected NSCLC cells. The C-terminal fragment (-C) of inhibited cell invasion and led to upregulation of and downregulation of in A549 and NCI-H1299 cells. Reduced expression was consistent with the decreased binding of transcription factor NF-kB to the promoter region in -C overexpressing cells. Based on the above results, we synthesized a cell-permeable peptide, CPP33-HADP ( active domain peptide), for lung-specific delivery and tested its therapeutic efficiency. CPP33-HADP effectively reduced the invasion ability of NSCLC cells in both in vitro and in vivo mouse models. Our results suggest that CPP33-HADP has significant potential for therapeutic applications in metastatic NSCLC.