Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as gefitinib are standard treatment of non-small cell lung cancer (NSCLC), but resistance often occurs. This study demonstrates that NSCLC cells resistant to gefitinib (GR cells) displayed a significantly higher microsomal prostaglandin E synthase-1 (mPGES-1) expression and activity than parental cells. Overexpression of mPGES-1/prostaglandin E-2 (PGE-2) signaling in GR cells was associated with acquisition of mesenchymal and stem-like cell properties, nuclear EGFR translocation and tolerance to cisplatin. mPGES-1 inhibition reduced mesenchymal and stem-like properties, and nuclear EGFR translocation in GR cells. Consistently, inhibition of mPGES-1 activity enhanced sensitivity to cisplatin and responsiveness to gefitinib in GR cells. We propose the mPGES-1/PGE-2 signaling as a potential target for treating aggressive and resistant lung cancers.
|Titolo:||mPGES-1 as a new target to overcome acquired resistance to gefitinib in non-small cell lung cancer cell lines|
MORBIDELLI, LUCIA (Corresponding)
DONNINI, SANDRA (Corresponding)
|Citazione:||Terzuoli, E., Costanza, F., Ciccone, V., Ziche, M., Morbidelli, L., & Donnini, S. (2019). mPGES-1 as a new target to overcome acquired resistance to gefitinib in non-small cell lung cancer cell lines. PROSTAGLANDINS & OTHER LIPID MEDIATORS, 143, 1-12.|
|Appare nelle tipologie:||1.1 Articolo in rivista|