Focal adhesion kinase (FAK) activation has been reported to be associated with cell progression and
metastasis in a wide variety of
cancer cells. Target treatment by inhibiting FAK has achieved remarkable effects in several
cancers, but the effect in
ovarian cancer has not been reported. In this study, we determined the role and the underlying molecular mechanism of BI853520, a novel small chemical FAK inhibitor against
ovarian cancer. Results show that phosphorylated FAK
tyrosine 397 (p-FAK Y397) is highly expressed in
ovarian cancer tumor tissues and cell lines (SKOV3 and OVCAR3). BI853520 treatment greatly suppresses cell proliferation, viability, migration, invasion, decreases anchorage-independent growth and motility in vitro. Besides, treatment with BI853520 increases biologic effects following combination with
chemotherapy in
ovarian cancer cell lines. In addition, BI853520 suppresses EMT in
ovarian cancer cell lines. Mechanically, BI853520 treatment downregulates the activation of PI3K/AKT/mTOR signal pathway. Finally, mice model experiments confirm BI853520 treatment dramatically reduces
tumor growth in vivo and suppresses the activation of PI3K/AKT/mTOR signal pathway. Taken together, our findings demonstrate that
focal adhesion kinase inhibitor BI853520 inhibits cell proliferation, migration, invasion and EMT process through PI3K/AKT/mTOR signaling pathway in
ovarian cancer, and BI853520 can offer a preclinical rationale for targeting repression of FAK in
ovarian cancer.