Anti-AKT2 (aa 455-468) polyclonal antibody

Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs. Dual luciferase reporter gene assay showed that miR-92a could specifically bind with the 3UTR of AKT2 and significantly repressed the luciferase activity. Down-regulation or up-regulation of miR-92a significantly increased or decreased the protein and phosphorylation levels of AKT2. siRNA-mediated down-regulation of AKT2 significantly prevented cell proliferation and migration of RA-FLSs, which were similar to the effects induced by overexpression of miR-92a. Moreover, AKT2 overexpression rescued miR-92a-mediated suppressive effect on proliferation and migration of RA-FLS. Thus, miR-92a could inhibit the proliferation and migration of RA-FLSs through regulation of AKT2 expression.

Purpose: To investigate the effect of combined inhibition of protein kinase B (AKT) and SRC on the growth and metastatic potential of human pancreatic cancer cells. Materials and Methods: AKT and SRC were inhibited using 10-DEBC and PP2, respectively. The expression of their messenger RNAs were down-regulated by specific small interfering RNA (siRNA). Changes in pancreatic cancer cell growth and metastatic potential were determined using a cell viability assay and a xenotransplant model of pancreatic cancer, as well as cell migration and invasion assays. Signal proteins were analyzed by Western blot. Results: The inhibitors 10-DEBC and PP2 suppressed cell proliferation in a dose-dependent fashion in pancreatic cancer cell lines MIA PaCa-2 and PANC-1. The simultaneous inhibition of AKT and SRC at low concentrations resulted in a significant suppression of cell proliferation. Knockdown of AKT2 and SRC using siRNAs also significantly decreased cell proliferation. In a pancreatic cancer model, combined treatment with 10-DEBC and PP2 also significantly suppressed the growth of pancreatic cancer. Application of 10-DEBC with PP2 significantly reduced the metastatic potential of pancreatic cancer cells by inhibiting migration and invasion. The combined inhibition suppressed the phosphorylation of mTOR and ERK in pancreatic cancer cells. Conclusion: Combined targeting of AKT and SRC resulted in a synergistic efficacy against human pancreatic cancer growth and metastasis.