Apigenin Inhibits UVB-Induced Skin Carcinogenesis: The Role of Thrombospondin-1 as an Anti-Inflammatory Factor.

摘要: We have previously demonstrated that apigenin promotes the expression of antiangiogenic protein thrombospondin-1 (TSP1) via a mechanism driven by mRNA-binding HuR. Here, we generated novel mouse model with whole-body THBS-1 gene knockout on SKH-1 genetic background, which allows studies UVB-induced acute skin damage and carcinogenesis tests TSP1 involvement in apigenin's anticancer effects. Apigenin significantly inhibited wild-type (WT) animals but not KO (TKO) mice, suggesting is critical component chemopreventive function cancer. Importantly, TKO mice presented elevated cutaneous inflammation at baseline, was manifested increased inflammatory infiltrates (neutrophils macrophages) levels two key cytokines, IL-6 IL-12. In agreement, maintaining normal UVB-irradiated WT using topical application caused marked decrease circulating cytokines. Finally, showed an altered population dynamics bone marrow myeloid progenitor cells (CD11b+), dramatic expansion neutrophil progenitors (Ly6ClowLy6Ghigh) compared to control. Our results indicate tumor suppressor mediator vivo effect skin, specifically its anti-inflammatory action.