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目的观察3,6-二羟黄酮对HER-2/neu高表达人乳腺癌细胞株MDA-MB-453移植瘤生长和miRNA表达谱的影响。方法以18只雌性BALB/c裸鼠建立乳腺癌MDA-MB-453细胞移植瘤模型,按照完全随机设计原则平均分入对照组和高、低剂量作用组,移植后72 h开始给予各处理因素,低、高剂量组分别以10、20 mg/(kg.d)的3,6-二羟黄酮灌胃,对照组以等量的生理盐水灌胃。每4天测量1次肿瘤体积和裸鼠体质量,处理28 d后取材,提取肿瘤组织总RNA并分离miRNA,样品采用PolyA Polymerase加尾后利用T4RNA连接酶将带有生物素标记的信号分子与之连接,进而与微阵列杂交,通过芯片扫描和数据分析获得miRNAs表达谱。结果高、低剂量组移植瘤生长速度低于对照组,肿瘤体积分别在处理12 d和16 d后显著低于对照组(P<0.05);处理24 d后高、低剂量组移植瘤质量均显著低于对照组(P<0.01)。miRNAs表达谱分析显示,高剂量组瘤组织miRNAs表达与对照组相比显著上调的有12个,显著下降的有15个。结论3,6-二羟黄酮可显著抑制人乳腺癌细胞株MDA-MB-453移植瘤的生长并影响其miRNAs表达谱。
Objective To observe the effect of 3,6-dihydroxyflavone on the growth and miRNA expression profile of HER-2 / neu overexpressing human breast cancer cell line MDA-MB-453. Methods Eighteen female BALB / c nude mice were used to establish the model of breast cancer MDA-MB-453 cell xenografts. The rats were equally divided into control group and high-dose group and low-dose group according to the completely random design principle. Each treatment group , Low dose group and high dose group were fed with 3,20-dihydroxyflavone at 10,20 mg / (kg · d), respectively. The control group was given gavage with normal saline. Tumor volume and body weight of nude mice were measured every 4 days. After 28 days of treatment, total RNA was extracted from the tumor tissues and miRNAs were isolated. Samples were polyclized with PolyA Polymerase and ligated with biotinylated signal molecules The miRNAs were then hybridized to microarrays and miRNAs expression profiles were obtained by chip scanning and data analysis. Results The tumor growth rate of the high and low dose groups was lower than that of the control group, the tumor volume was significantly lower than that of the control group on the 12th day and the 16th day after treatment (P <0.05) Significantly lower than the control group (P <0.01). miRNAs expression profile analysis showed that miRNAs expression in high-dose group was significantly up-regulated compared with the control group, 12, a significant decrease of 15. Conclusion 3,6-dihydroxyflavone can significantly inhibit the growth of human breast cancer cell line MDA-MB-453 and affect its miRNAs expression profile.