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33?and?34 Enforced expression of miR-92a significantly inhibited integrin ��5 expression and the tyrosine phosphorylation of FAK, followed by the down-regulation of MMP-2, which is known to play a major role in ovarian cancer invasion (Figure?5, F and G). Given that enforced expression of miR-92a inhibited the adhesion, invasion, and proliferation of ovarian cancer cells by inhibiting integrin ��5 expression, we examined the therapeutic potential of enforced expression of miR-92a in an ovarian cancer xenograft model. Lentiviruses containing the precursor of miR-92a (Figure?6A) or scrambled miRNA (control miRNA) were obtained and stably transduced into HeyA-8 cells. High and stable transduction efficiency (>90%) was confirmed by the red fluorescent puromycin-N-acetyl-transferase from the Lenti-miRNA-vector (Biosettia) (Figure?6B). The enforced expression of Tasisulam miR-92a (Figure?6C) and the subsequent down-regulation of integrin ��5 expression (Figure?6D) were confirmed. In?vitro cell proliferation was assessed by culturing transduced HeyA-8 cells onto fibronectin and collagen type 1. Enforced expression of miR-92a inhibited the cell proliferation of HeyA-8 cells when plated onto fibronectin ( Figure?6E). Two weeks after the i.p. ISRIB solubility dmso inoculation of HeyA-8 cells, mice showed multiple tumors on the peritoneal surface, omentum, small-bowel mesentery, and both ovaries. Integrin ��5 expression and the tyrosine phosphorylation of FAK (Tyr 861) were inhibited in the tumor nodules of the mice inoculated with cells overexpressing miR-92a compared with those inoculated with control ( Figure?6F). Western blot analysis of the lysates from the inoculated nodules revealed that a 65% reduction of integrin ��5 expression Inhibitor Library was induced by miR-92a overexpression ( Figure?6G). The number of metastases and the tumor burden were significantly inhibited in mice inoculated with cells that overexpressed miR92a compared with controls (number of metastases: miR-92a, 54.0 �� 23.0; control, 126.0 �� 20.4; tumor weight: miR-92a, 0.46 �� 0.21 g; control, 1.42 �� 0.31 g) (P