Intraperitoneal Administration of Synthetic MicroRNA-214 Exhibits Tumor Suppression in an Intraperitoneal Dissemination Mouse Model of Canine Hemangiosarcoma

Abstract Canine hemangiosarcoma (HSA) has extremely poor prognosis, making it necessary to develop new systemic treatment methods. MicroRNA-214 (miR-214) is one of many microRNAs (miRNA) that can induce apoptosis in HSA cell lines. Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. In this study, we evaluated the effects of miR-214/5AE on stage 2 HSA in a mouse model. Mice intraperitoneally administered with miR-214/5AE (5AE group) had significantly fewer intraperitoneal dissemination tumor foci (median number: 80 vs. 233; p < 0.05) and lighter median foci weight (0.26 g vs. 0.74 g; p < 0.05). There was an increase in p53 and cleaved caspase-3 expression in the 5AE group. The mice in this group also had a significantly lower proportion of Ki-67-positive cells than those in the non-specific miR group. Notably, there were no significant side effects observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in the intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. We strongly believe that miR-214/5AE could be a novel miRNA-based chemotherapeutic agent capable of improving the prognosis of HSA.