Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma |
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Authors: | Yoshikawa Ryutaro Maeda Atsushi Ueno Yoshihito Sakai Hiroki Kimura Shintaro Sawadaishi Tomohiro Kohgo Satoru Yamada Kohei Mori Takashi |
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Institution: | 1.The United Graduate School of Veterinary Sciences, Gifu University, Gifu, Gifu, 501-1193, Japan ;2.Laboratory of Veterinary Clinical Oncology, Joint Department of Veterinary Medicine, Gifu University, Gifu, Gifu, 501-1193, Japan ;3.Course of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, Gifu, 501-1193, Japan ;4.United Graduate School of Agricultural Science, Gifu University, Gifu, Gifu, 501-1193, Japan ;5.Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, Gifu, Gifu, 501-1193, Japan ;6.Department of Veterinary Pathology, Faculty of Applied Biological Sciences, Gifu University, Gifu, Gifu, 501-1193, Japan ;7.Biochemicals Division, Yamasa Corporation, Choshi, Chiba, 288-0816, Japan ; |
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Abstract: | Canine hemangiosarcoma (HSA) has an 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: 72.5 vs. 237.5; p?<?0.05) and a lower median foci weight (0.26 g vs. 0.61 g; p?<?0.05). Mice in the 5AE group had increased expression of p53 and cleaved caspase-3, and a significantly lower proportion of Ki-67-positive cells, than those in the non-specific miR group. Notably, no significant side effects were observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in an intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. These results provide a basis for future studies on the antitumor effect of miR-214/5AE for HSA. |
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