Sakuda Tomohiko, Kubo Tadahiko, Johan Muhammad Phetrus, Furuta Taisuke, Sakaguchi Takemasa, Adachi Nobuo
Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan;
Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Anticancer Res. 2023 Mar;43(3):1185-1191. doi: 10.21873/anticanres.16264.
BACKGROUND/AIM: Attempts have been made to enhance treatment with vesicular stomatitis virus (VSV) for osteosarcoma. We have previously shown that VSV incorporated with miRNA143 enhanced the antitumor effect at some doses; however, the range of the doses was narrow. This has not been evaluated in vivo, and the synergistic effect of this antitumor effect in animals is unknown. The purpose of the study was to evaluate the oncolytic effect of VSV-miRNA on osteosarcoma cells in vivo.
A novel oncolytic VSV was developed by incorporating the tumor-suppressor microRNA143 (rVSV-miR143). In order to compare the antitumor effects of administration methods (intravenous and intratumoral administration) of rVSV-miR143 with those of VSV, a comparative analysis of primary tumor volume, metastatic lesions and survival rate was performed in mouse models of osteosarcoma.
Following intratumoral injection, rVSV-miR143 showed a significant reduction in primary tumor volume, but no significant difference was observed in metastatic lesions and survival rate compared to VSV. Following intravenous injection, rVSV-miR143 revealed no significant difference in primary tumor volume, metastatic lesion and survival rate compared to VSV.
VSV incorporating tumor-suppressor miRNA143 demonstrated a slightly synergistic antitumor effect on osteosarcoma in vivo.
背景/目的：人们一直在尝试增强水泡性口炎病毒（VSV）对骨肉瘤的治疗效果。我们之前已经表明，与miRNA143结合的VSV在某些剂量下增强了抗肿瘤作用；然而，剂量范围较窄。这尚未在体内进行评估，且这种抗肿瘤作用在动物体内的协同效应尚不清楚。本研究的目的是评估VSV-miRNA对骨肉瘤细胞的体内溶瘤作用。
通过整合肿瘤抑制性微小RNA143（rVSV-miR143）开发了一种新型溶瘤性VSV。为了比较rVSV-miR143与VSV给药方法（静脉内和瘤内给药）的抗肿瘤效果，在骨肉瘤小鼠模型中对原发肿瘤体积、转移灶和生存率进行了比较分析。
瘤内注射后，rVSV-miR143显示原发肿瘤体积显著减小，但与VSV相比，转移灶和生存率无显著差异。静脉注射后，rVSV-miR143与VSV相比，原发肿瘤体积、转移灶和生存率无显著差异。
整合肿瘤抑制性miRNA143的VSV在体内对骨肉瘤显示出轻微的协同抗肿瘤作用。
