Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer
| Autor: | Yizhi Gao, Chenchen Ren, Hong Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
endocrine system diseases Endocrinology Diabetes and Metabolism Cell Metastasis Focal adhesion Endocrinology Ovarian cancer medicine PI3K/AKT/mTOR BI853520 Protein kinase B RC254-282 PI3K/AKT/mTOR pathway Endocrine and Autonomic Systems Chemistry Cell growth Research EMT Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease medicine.anatomical_structure Oncology Cancer cell Cancer research |
| Zdroj: | Discover. Oncology Discover Oncology, Vol 12, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2730-6011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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