Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma
Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma
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DOI：
10.1007/s11259-021-09869-1
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发表时间：
2022-01-06
影响因子：
2.2
通讯作者：
Mori, Takashi
中科院分区：
文献类型：
--
作者：
Yoshikawa, Ryutaro;Maeda, Atsushi;Mori, Takashi
犬血管肉瘤（HSA）预后极差，因此有必要开发新的系统治疗方法。microRNA-214（miR-214）是众多能诱导人血清白蛋白细胞凋亡的microRNA（miRNA）之一。合成的miR-214（miR-214/5AE）显示出比成熟的miR-214更高的细胞毒性和更强的核酸酶抗性，已被开发用于临床应用。在这项研究中，我们在小鼠模型中评估了miR-214/5AE对2期HSA的影响。腹膜内施用miR-214/5AE的小鼠（5AE组）具有显著更少的腹膜内播散肿瘤病灶（中值数目：72.5对237.5; p < 0.05）和更低的中值病灶重量（0.26 g对0.61 g; p < 0.05）。与非特异性miR组相比，5AE组小鼠的p53和切割的caspase-3表达增加，Ki-67阳性细胞的比例显著降低。值得注意的是，没有观察到显著的副作用。这些结果表明，腹膜内施用miR-214/5AE通过诱导细胞凋亡和抑制细胞增殖在HSA的腹膜内播散小鼠模型中表现出抗肿瘤作用。这些结果为进一步研究miR-214/5AE对HSA的抗肿瘤作用提供了基础。
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.