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RhoC 沉默对裸鼠多发性骨髓瘤异种移植物和血管生成的影响。

Effect of RhoC silencing on multiple myeloma xenografts and angiogenesis in nude mice.

机构信息

Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Tumor Pathology, Zhengzhou, China.

Department of Urinary Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

J Biol Regul Homeost Agents. 2019;33(5):1387-1394.

Abstract

In this study, we investigated the expression of RhoC in the multiple myeloma (MM) cell line RPMI- 8226, as well as the effects of silencing RhoC on the growth of tumor xenografts and tumor-induced angiogenesis in nude mice with MM. For this purpose, we transduced RPMI-8226 cells with lentiviral particles overexpressing short hairpin RNAs (shRNA) targeting RhoC. Tumor xenografts were generated by subcutaneously injecting nude mice with RPMI-8226 cells overexpressing control shRNA [negative control (NC) group] or the RhoC shRNA [the experimental (S) group], respectively. RhoC protein and mRNA levels in the tumor xenografts were measured. Nude mice were also subcutaneously inoculated with Matrigel mixed with vascular endothelial growth factor, and CD31 and KI67 levels in the tumor xenografts were measured by immunohistochemistry. Similarly, we assessed tumor xenograft growth and angiogenesis in Matrigel implants in the mice of both groups. We found that RhoC levels, microvessel density, and CD31 labeling index were more reduced in the S group than in the NC group. However, there was no significant difference in the size of tumor xenografts between the 2 groups. The number of new vessels and the neovascular length in the Matrigel implants were significantly lower in the S group than in the NC group. Therefore, we concluded that RhoC expression in myeloma xenografts has important effects on the induction of angiogenesis.

摘要

在这项研究中,我们研究了 RhoC 在多发性骨髓瘤(MM)细胞系 RPMI-8226 中的表达,以及沉默 RhoC 对 MM 裸鼠肿瘤异种移植和肿瘤诱导血管生成的生长的影响。为此,我们用靶向 RhoC 的短发夹 RNA(shRNA)过表达慢病毒颗粒转导 RPMI-8226 细胞。通过皮下注射 RPMI-8226 细胞过表达对照 shRNA[阴性对照(NC)组]或 RhoC shRNA[实验组(S)组]分别在裸鼠中生成肿瘤异种移植。测量肿瘤异种移植中 RhoC 蛋白和 mRNA 水平。裸鼠还皮下接种与血管内皮生长因子混合的 Matrigel,并通过免疫组织化学测量肿瘤异种移植中 CD31 和 KI67 水平。同样,我们评估了两组小鼠 Matrigel 植入物中的肿瘤异种移植生长和血管生成。我们发现 S 组的 RhoC 水平、微血管密度和 CD31 标记指数均低于 NC 组。然而,两组之间肿瘤异种移植的大小没有显著差异。S 组中 Matrigel 植入物中的新血管数量和新生血管长度明显低于 NC 组。因此,我们得出结论,骨髓瘤异种移植中 RhoC 的表达对血管生成的诱导有重要影响。

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