Reversal of EGFR inhibitors' resistance by co-delivering EGFR and integrin αvß3 inhibitors with nanoparticles in non-small cell lung cancer.
Biosci Rep
; 39(8)2019 08 30.
Article
in En
| MEDLINE
| ID: mdl-31316001
ABSTRACT
Purpose:
Tumor cells, with drug resistance, are associated with failed treatment and poor prognosis. Our aim was to explore potential strategy to overcome the epidermal growth factor receptor (EGFR) inhibitors resistance in non-small cell lung cancer (NSCLC).Materials andmethods:
Flow cytometry was used to examine and sort cells. Using MTT assay, we detected the cell viability under different conditions. Using RT-qPCR and Western blot, we determined the targeted gene expression in mRNA and protein levels. The morphology of the prepared nanoparticles was pictured by transmission electron microscopy. We also performed immunohistochemistry (IHC) and immunofluorescence (IF) to detect the proteins expression. Subcutaneous cancer models in nude mice were constructed to evaluate the anti-cancer effects in vivoResults:
Here, we observed enhanced expression of integrin αvß3 in tumor tissues from EGFR inhibitors resistant patients. Also, integrin αvß3-positive NSCLC cells revealed significant EGFR inhibitors resistance, resulting from the activation of Galectin-3/KRAS/RalB/TBK1/NF-κB signaling pathway. Co-encapsulating integrin αvß3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity.Conclusion:
Our results demonstrated that co-encapsulation of erlotinib and cilengitide by MPEG-PLA (Erlo+Cilen/PP) nanoparticles revealed enhanced tumor suppression along with reduced organ damages, providing an innovative approach for NSCLC treatment.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Integrin alphaVbeta3
/
Nanoparticles
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Biosci Rep
Year:
2019
Type:
Article
Affiliation country:
China