Journal
DISCOVER ONCOLOGY
Volume 12, Issue 1, Pages -Publisher
SPRINGER
DOI: 10.1007/s12672-021-00425-6
Keywords
BI853520; Ovarian cancer; PI3K; AKT; mTOR; EMT
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Funding
- Science and technology project in Henan province [162102310131]
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The study found that the FAK inhibitor BI853520 suppresses cell proliferation, migration, invasion, and EMT process in ovarian cancer cells through the PI3K/AKT/mTOR signaling pathway. In vivo experiments confirmed that BI853520 treatment significantly reduced tumor growth and suppressed the activation of the signaling pathway.
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.
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