FAK inhibitor PF-562271 inhibits the migration and proliferation of high-grade serous ovarian cancer cells through FAK and FAK mediated cell cycle arrest.

Abstract

Focal adhesion kinase (FAK) is a promising therapeutic target for various cancers and its inhibitor development is in full swing. PF-562271 is a classic FAK inhibitor that has shown promising preclinical data and has been found to exhibit an anti-migration effect on some cancer cells. However, its anticancer effect on high-grade serous ovarian cancer (HGSOC) has not been reported. In this study, we evaluated the anti-migration and anti-proliferation effects of PF-562271 against HGSOC SKOV3 and A2780 cells, as well as the underlying mechanism. The results demonstrated that FAK was overexpressed in clinical HGSOC tissues and was positively correlated with the pathological progression of HGSOC. Moreover, HGSOC patients with high FAK expression levels exhibited low survival rates. PF-562271 treatment significantly inhibited the cell adhesion and migration of SKOV3 and A2780 cells by inhibiting p-FAK expression and decreasing the FA surface area. Additionally, PF-562271 treatment inhibited colony formation and induced cell senescence through G1 phase cell cycle arrest mediated DNA replication inhibition. Taken together, the findings demonstrated that FAK inhibitor PF-562271 significantly inhibits HGSOC cell adhesion, migration, and proliferation process through FAK and/or FAK mediated cell cycle arrest, and suggested that PF-562271 could serve as a potential oncotherapeutic agent for HGSOC targeting treatment.