상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

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

Authors 

S M SonJ YunS H LeeH S HanY H LimC G WooH C LeeH G SongY M GuHyun-Jun LeeO J Lee

Publisher 

Nature Publishing Group

Issue Date 

2019

Citation 

Scientific Reports

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.

URI 

https://doi.org/10.1038/s41598-019-48104-5

ISSN 

2045-2322

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-10-29


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)