The molecular mechanism of baicalein repressing progression of gastric cancer mediating miR-7/FAK/AKT signaling pathway

Abstract

BackgroundBaicalein (BAI) has a significant anti-cancerous function in the treatment of gastric cancer (GC). Focal adhesion kinase (FAK) is a key regulatory molecule in integrin and growth factor receptor mediated signaling. MicroRNA-7 (miR-7), has been considered as a potential tumor suppressor in a variety of cancers. However, the possible mechanisms by which BAI inhibiting progression of gastric cancer mediating miR-7/FAK/AKT signaling pathway remain unclear. PurposeTo investigate the molecular mechanism and effects of BAI inhibiting progression of gastric cancer mediating miR-7/FAK/AKT signaling pathway. MethodsGastric cancer cell lines with FAK knockdown and overexpression were constructed by lentivirus transfection. After BAI treatment, the effects of FAK protein on proliferation, metastasis and angiogenesis of gastric cancer cells were detected by MTT, EdU, colony formation, wound healing, transwell and Matrigel tube formation assays. In vivo experiment was performed by xenograft model. Immunofluorescence and western blot assay were used to detect the effects of FAK protein on the expression levels of EMT markers and PI3K/AKT signaling pathway related proteins. qRT-PCR and luciferase reporter assay were used to clarify the targeting relationship between miR-7 and FAK. ResultsBAI can regulate FAK to affect proliferation, metastasis and angiogenesis of gastric cancer cells through PI3K/AKT signaling pathway. qRT-PCR showed BAI can upregulated the expression of miR-7 and luciferase reporter assay showed the targeting relationship between miR-7 and FAK. Additionally, miR-7 mediates cell proliferation, metastasis and angiogenesis by directly targeting FAK 3′UTR to inhibit FAK expression. ConclusionBAI repressing progression of gastric cancer mediating miR-7/FAK/AKT signaling pathway.