溶血磷脂酸与Hippo-Yes相关蛋白在促进三阴性乳腺癌细胞MDA-MB-231侵袭转移的信号通路研究

发布时间：2018-04-28 13:19

本文选题：乳腺癌 + 溶血磷脂酸　；参考：《医学研究生学报》2017年08期

【摘要】：目的三阴性乳腺癌作为乳腺癌的特殊类型,尚缺乏有效的靶向治疗手段。文中旨在观察溶血磷脂酸(LPA)对三阴性乳腺癌的影响,探讨LPA-Hippo-Yes相关蛋白(YAP)信号通路在促进三阴性乳腺癌侵润转移中的作用及机制。方法体外合成YAP序列特异性小干扰RNA,应用质粒转染MDA-MB-231乳腺癌细胞株为实验组,非特异性siRNA转染MDA-MB-231细胞为阳性对照组,未转染MDA-MB-231细胞为空白对照组,每组设2个平行孔。检测各组对Hippo-YAP信号的影响,其作用机制及对Hippo-YAP上、下游信号通路调控。结果实验组总蛋白中YAP含量、细胞转染48h后的侵袭、转移能力[(0.035±0.005)、(2.200±1.000)个、(3.500±0.800)个]较阳性对照组[(0.343±0.012)、(27.600±5.100)个、(22.300±5.000)个]、空白对照组[(0.384±0.017)、(26.500±4.800)个、(22.350±6.000)个]明显降低(P0.05)。实验组60、120、240 min时YAP表达量较阳性对照组、空白对照组显著降低(P0.05)。实验组10、20、50μmol/L的YAP相对表达量显著低于阳性对照组、空白对照组(P0.05)。C3转移酶和Y27632分别干预后,实验组p YAP mRNA含量(0.255±0.052、0.326±0.017)与空白对照组((0.048±0.032、0.534±0.017)、阳性对照组(0.052±0.021、0.528±0.024)比较差异有统计学意义(P0.05)。实验组YAP m NA、AREG m NA的表达量(0.176±0.032、0.263±0.008)较空白对照组(0.043±0.013、0.051±0.014)、阴性对照组(0.049±0.025、0.057±0.043)显著升高(P0.05)。结论 LPA诱导乳腺癌细胞侵袭转移,具有YAP蛋白依赖性,并具有时间与浓度依赖的特点;LPA-Hippo-YAP信号传导通路可能是促进三阴性乳腺癌细胞长时间转移的机制之一。
[Abstract]:Objective as a special type of breast cancer, triple negative breast cancer lacks effective targeted therapy. The purpose of this study was to observe the effect of lysophosphatidic acid (LPA) on triple-negative breast cancer and to explore the role and mechanism of LPA-Hippo-Yes associated protein (Yap) signaling pathway in promoting invasion and metastasis of triple-negative breast cancer. Methods YAP sequence specific small interference RNAs were synthesized in vitro. MDA-MB-231 breast cancer cell lines were transfected with plasmids as experimental group, MDA-MB-231 cells transfected with nonspecific siRNA as positive control group, and untransfected MDA-MB-231 cells as blank control group. Each group was divided into two parallel holes. The effect of each group on Hippo-YAP signal, its mechanism and regulation of Hippo-YAP upstream and downstream signal pathway were detected. Results the YAP content in the total protein, invasion and metastasis ability of the cells in the experimental group [0.035 卤0.005, 2.200 卤1.000] were significantly lower than those in the positive control group [0.343 卤0.012, 27.600 卤5.100] and the blank control group [0.384 卤0.017, 26.500 卤4.800, 22.350 卤6.000], respectively, which were significantly lower than those in the positive control group (0.343 卤0.012, 27.600 卤5.100) and the blank control group, [0.384 卤0.017, 26.500 卤4.800, 22.350 卤6.000]. The expression of YAP in the experimental group was significantly lower than that in the positive control group at 60120240 min, while that in the blank control group was significantly lower than that in the control group. The relative expression of YAP at 50 渭 mol/L in the experimental group was significantly lower than that in the positive control group. After the intervention of P0.05N. C3 transferase and Y27632 in the blank control group, the p YAP mRNA content of the experimental group was 0.255 卤0.052 卤0.052 卤0.017) and that of the blank control group was 0.048 卤0.032, 0.534 卤0.017, and the positive control group was 0.052 卤0.021, 0.528 卤0.024). The expression of YAP m NAA mRNA in the experimental group (0.176 卤0.032) was significantly higher than that in the blank control group (0.043 卤0.013) and the negative control group (0.049 卤0.025, 0.057 卤0.043), which was significantly higher than that in the blank control group (0.043 卤0.014) and the negative control group (0.049 卤0.025, 0.057 卤0.043). Conclusion LPA induces invasion and metastasis of breast cancer cells, which is YAP protein-dependent and time-and concentration-dependent. LPA-Hippo-YAP signal transduction pathway may be one of the mechanisms of promoting long-term metastasis of triple-negative breast cancer cells.
【作者单位】：西安交通大学医学院附属汉中三二0一医院肿瘤科;西安交通大学医学院附属第一医院肿瘤外科;长安大学医学院校医院乳腺外科;陕西省人民医院肿瘤外科;
【基金】：西安交通医学院附属三二0一医院重点基金项目(3201YK201539)
【分类号】：R737.9

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