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.
Methods
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 αvβ3 in tumor tissues from EGFR inhibitors resistant patients. Also, integrin αvβ3-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 αvβ3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity.
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 and
Results
Here, we observed enhanced expression of integrin αvβ3 in tumor tissues from EGFR inhibitors resistant patients. Also, integrin αvβ3-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 αvβ3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity.