Locostatin is a potent and cell permeable inhibitor of Raf kinase inhibitor protein (RKIP)/Raf1 kinase interaction and an inhibitor of cell migration.

Locostatin treatment resulted in the activation of the mitogen-activated protein kinase (MAPK) signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol.?Further, RKIP inhibition by locostatin reduces ECM components.?Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells.?Finally, locostatin treatment reduced GSK3β expression.?Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells[1].

Compared to the CCl4 group, HYP (208.56 ± 6.12) μg/g, percentage of total collagen at overall region (1.91 ± 0.13), MMP-13/TIMP-1 (0.19 ± 0.01), MPO (1.45 ± 0.04) U/g, TGF-β (2652 ± 91.20), PDGF-AA (3897 ± 290.69), and E-selectin (1569 ± 66.48) in the liver tissues were decreased significantly in the locostatin-treated group[2].

Carbon tetrachloride (CCl4) was used to induce liver fibrosis in mice, and locostatin was injected intraperitoneally. Liver fibrosis was assessed by Masson and Sirius red staining, hydroxyproline (HYP) assay, and collagen percentage area. Collagen I, collagen III, and α-SMA were detected by RT-PCR and western blot. The levels of MMP-13, MMP-2, TIMP-1, and TIMP-2 were estimated by ELISA. Liver inflammation was evaluated by HE staining and immunohistochemistry; liver myeloperoxidase (MPO), superoxide dismutase, and malondialdehyde were measured by ELISA; and cytokines were by Mouse Cytokine Array Q4000[2]