Therapeutic effect of pHLIP-mediated CEACAM6 gene silencing in lung adenocarcinoma

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Title
Therapeutic effect of pHLIP-mediated CEACAM6 gene silencing in lung adenocarcinoma
Author(s)
S M Son; J Yun; S H Lee; H S Han; Y H Lim; C G Woo; H C Lee; H G Song; Y M Gu; Hyun-Jun Lee; O J Lee
Bibliographic Citation
Scientific Reports, vol. 9, pp. 11607-11607
Publication Year
2019
Abstract
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays an important role in lung cancer progression. Here, we examined the therapeutic efficacy of CEACAM6 gene silencing using an siRNA delivery platform targeting the acidic tumour microenvironment in a lung adenocarcinoma xenograft mouse model. An siRNA delivery vector was constructed by tethering the peptide nucleic acid form of an siRNA targeting CEACAM6 (siCEACAM6) to a peptide with a low pH-induced transmembrane structure (pHLIP) to transport siRNAs across the plasma membrane. Specific binding of the pHLIP-siCEACAM6 conjugate to A549 lung adenocarcinoma cells at low pH was demonstrated by flow cytometry. A549 cells incubated with pHLIP-siCEACAM6 at an acidic pH showed downregulated expression of endogenous CEACAM6 protein and reduced cell viability. The in vivo tumour-suppressing effects of pHLIP-siCEACAM6 in lung adenocarcinoma were assessed in a xenograft model generated by injecting BALB/c nude mice with A549 cells. pHLIP-siCEACAM6 treatment alone resulted in tumour growth inhibition of up to 35.5%. When combined with cisplatin treatment, pHLIP-siCEACAM6 markedly enhanced tumour growth inhibition by up to 47%. In conclusion, the delivery of siCEACAM6 to lung adenocarcinoma using the pHLIP peptide has therapeutic potential as a unique cancer treatment approach.
ISSN
2045-2322
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41598-019-48104-5
Type
Article
Appears in Collections:
Ochang Branch Institute > Natural Product Research Center > 1. Journal Articles
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