15-氧代绣线菊内酯对人肾细胞癌ACHN细胞裸鼠移植瘤生长的影响

发布时间：2019-02-13 13:15

【摘要】：目的肾细胞癌是一种常见恶性肿瘤,化疗和放疗效果均不佳。Wnt信号通路在肾细胞癌的发生,增殖及凋亡等方面起到至关重要的作用。文中旨在研究一种新型小分子wnt信号抑制剂15-氧代绣线菊内酯(NC043)对小鼠肾细胞癌模型的抑制作用。方法将1×107的ACHN人肾癌细胞株在100μL的PBS中混匀,接种于BALB/c雌性裸鼠背部右后侧皮下制作移植瘤模型。成瘤裸鼠按随机列表法分为阴性对照组、NC043 45μg/kg组和NC043 90μg/kg组,后2组按不同浓度NC043溶解于含3%二甲基亚砜DMSO的磷酸盐缓冲液PBS中。3组各连续腹腔注射NC043 15天,第16天处死小鼠。检测各组小鼠的体重和肿瘤体积变化,用免疫组化检测肿瘤细胞的ki67、TCF4和β-catenin表达情况。结果 NC043使得小鼠的肿瘤生长速度明显减缓,体积明显减小,NC043 45μg/kg组和NC043 90μg/kg组抑瘤率分别为36.4%和56.4%,与阴性对照组(0)差异均有统计学意义(P0.05)。免疫组化检测表明,NC043 90μg/kg组ki67、TCF4、β-catenin表达呈弱阳性,NC04345μg/kg组呈阳性,而阴性对照组呈强阳性。结论 NC043能够有效地抑制肾癌细胞ACHN细胞裸鼠移植瘤的生长,并且抑制Wnt信号通路的相关蛋白的表达,具有潜在的靶向治疗肾癌的作用。
[Abstract]:Objective Renal cell carcinoma (RCC) is a common malignant tumor, and the effect of chemotherapy and radiotherapy is poor. Wnt signaling pathway plays an important role in the development, proliferation and apoptosis of renal cell carcinoma. The aim of this study was to investigate the inhibitory effect of a novel small molecular wnt signal inhibitor, 15-oxomethylanilactone (NC043), on mouse renal cell carcinoma (RCC) model. Methods 1 脳 10 ~ 7 ACHN human renal cell carcinoma cell line was mixed in 100 渭 L PBS and inoculated into the right posterior subcutaneous of BALB/c female nude mice to make transplanted tumor model. Nude mice were randomly divided into three groups: negative control group, NC043 45 渭 g/kg group and NC043 90 渭 g/kg group. The latter two groups were dissolved in the phosphate buffer PBS containing 3% dimethylsulfoxide DMSO at different concentrations. NC043 was injected intraperitoneally for 15 days in each group. Mice were killed on the 16th day. The expression of ki67,TCF4 and 尾-catenin in tumor cells were detected by immunohistochemistry. Results the tumor growth rate and volume of mice were significantly slowed down by NC043. The tumor inhibition rates of NC043 45 渭 g/kg group and NC043 90 渭 g/kg group were 36.4% and 56.4%, respectively, which were significantly different from those of negative control group (P0.05). The expression of ki67,TCF4, 尾-catenin was weakly positive in NC043 90 渭 g/kg group, positive in NC04345 渭 g/kg group and strongly positive in negative control group. Conclusion NC043 can effectively inhibit the growth of renal cancer cell ACHN xenografts in nude mice and inhibit the expression of related proteins in Wnt signaling pathway, which may be a potential target therapy for renal cell carcinoma.
【作者单位】：南京大学医学院附属金陵医院(南京军区南京总医院)泌尿外科;
【基金】：国家自然科学基金(81372742)
【分类号】：R737.11

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