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

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.