miR-106a 对小鼠卵巢癌移植瘤生长的影响研究

Effect of intratumoral injection of miR-106a inhibitor on tumor growth of ovarian cancer xenografts in mice

摘要:

目的 研究miR-106a 对小鼠卵巢癌移植瘤生长的影响。方法 选择SPF 级BALB/c 小鼠作为实 验动物，将SKOV3 卵巢癌细胞注入小鼠皮下以复制卵巢癌移植瘤模型，将模型小鼠随机分为空白对照组、阴性 对照组、miR-106a 抑制组，分别用不含抑制剂的转染试剂、含阴性对照抑制剂的转染试剂、含miR-106a 抑 制剂的转染试剂进行干预，干预前及干预后分别测定移植瘤体积以及移植瘤中PTEN 信号通路分子的表达量。 结果 干预后10、20、30 和40 d 时，空白对照组、阴性对照组、miR-106a 抑制组之间瘤体体积的比较差异有 统计学意义（P <0.05），每组内不同时间点的比较差异有统计学意义（P <0.05），组间与时间变化趋势的比较 差异有统计学意义（P <0.05）；干预后40 d 时，miR-106a 抑制组小鼠肿瘤组织中PTEN 的mRNA 表达高于 空白对照组和阴性对照组，PI3K、AKT、CyclinD1、Survivin、MMP-2、MMP-9、VEGF 的mRNA 表达低 于空白对照组和阴性对照组。结论 miR-106a 对小鼠卵巢癌移植瘤的生长具有抑制作用，增强PTEN 信号通 路是miR-106a 抑制肿瘤生长的分子机制。

Abstract:

Objective To study the effect of intratumoral injection of miR-106a inhibitor on tumor growth of ovarian cancer xenografts in mice. Methods SPF BALB/c mice were selected as the experimental animal, then ovarian cancer xenograft model was made by injection of ovarian cancer SKOV3 cells into nude mice. The model mice were randomly divided into a blank control group, a negative control group and a miR-106 inhibition group, intervented respectively by transfection of reagent containing no inhibitor, transfection of reagent containing negative control inhibitors and transfection of reagent containing miR-106a inhibitor. Before and after intervention, the xenograft volume and expressions of PTEN signaling molecules in the xenografts were measured. Results On the 10th, 20th, 30th and 40th d after intervention, there were significant differences in the tumor volume among the 3 groups (P < 0.05), and there were significant differences in the tumor volume at different time points in each group (P < 0.05). The change trends of the tumor volume with time had statistical differences among the 3 groups (P < 0.05). On the 40th d after intervention, PTEN mRNA expression level of the miR-106a inhibition group was significantly higher than that of the blank control group and the negative control group (P < 0.05), while the mRNA expression levels of PI3K, AKT, Cyclin D1, Survivin, MMP-2, MMP-9 and VEGF were significantly lower than those of the blank control group and the negative control group (P < 0.05). Conclusions Intratumoral injection of miR-106a inhibitor has inhibitory effect on tumor growth of ovarian cancer xenografts in mice, and the enhancement of PTEN signaling pathway is the molecular mechanism of tumor growth inhibition by miR-106a inhibitor.