A synthetic CPP33-conjugated HOXA9 active domain peptide inhibits invasion ability of non-small lung cancer cells

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Title
A synthetic CPP33-conjugated HOXA9 active domain peptide inhibits invasion ability of non-small lung cancer cells
Author(s)
S L Yu; Han Koo; S I Lee; J Kang; Y H Han; Young Il Yeom; Dong Chul Lee
Bibliographic Citation
Biomolecules, vol. 10, no. 11, pp. 1589-1589
Publication Year
2020
Abstract
Homeobox A9 (HOXA9) expression is associated with the aggressive growth of cancer cells and poor prognosis in lung cancer. Previously, we showed that HOXA9 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 HOXA9 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 (HOXA9-C) of HOXA9 inhibited cell invasion and led to upregulation of CDH1 and downregulation of SNAI2 in A549 and NCI-H1299 cells. Reduced SNAI2 expression was consistent with the decreased binding of transcription factor NF-kB to the SNAI2 promoter region in HOXA9-C overexpressing cells. Based on the above results, we synthesized a cell-permeable peptide, CPP33-HADP (HOXA9 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.
Keyword
HOXA9CPP33-HADPSNAI2cell invasionnon-small cell lung cancer
ISSN
2218-273X
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/biom10111589
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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