17β-雌二醇对乳腺癌细胞迁移的影响及CANP-FN通路的介导作用

发布时间：2018-04-20 10:30

本文选题：β-雌二醇 + 钙蛋白酶　；参考：《中国药理学通报》2017年10期

【摘要】：目的探讨17β-雌二醇(E2)对人乳腺癌细胞迁移活动的影响及其信号机制。方法以雌激素受体(ER)阳性MCF-7和ER阴性MDA-MB-468乳腺癌细胞为研究模型,E2处理诱导细胞迁移。采用划痕实验检测细胞迁移能力,小分子RNA(siRNA)转染模型细胞沉默纤连蛋白(FN)基因表达,Western blot法检测蛋白水平,钙蛋白酶(CANP)特异性抑制剂Calpeptin(Cal)预处理细胞干预胞内CANP活性。结果(1)E2(50 nmol·L~(-1))处理24 h可明显促进MCF-7和MDA-MB-468乳腺癌细胞迁移,迁移率分别增加(51.55±5.50)%(P0.05)和(40.78±4.78)%(P0.01);(2)E2明显上调MCF-7和MDA-MB-468乳腺癌细胞FN蛋白表达水平,分别为对照组的2.11倍(P0.05)和1.86倍(P0.01);(3)Cal(10μmol·L~(-1))可明显抑制E2诱导的MCF-7和MDA-MB-468乳腺癌细胞迁移,抑制率分别为(49.55±6.44)%(P0.05)和(36.85±4.40)%(P0.01);(4)Cal能明显抑制MCF-7和MDA-MB-468乳腺癌细胞FN蛋白表达上调,抑制率分别为(80.12±4.55)%和(78.84±5.70)%(P0.01);(5)siRNA沉默FN能抑制E2诱导MCF-7和MDA-MB-468乳腺癌细胞迁移,抑制率分别为(40.65±5.80)%(P0.01)和(40.88±6.02)%(P0.05)。结论E2可促进ER阳性或阴性乳腺癌细胞的迁移,而CANP-FN信号通路可能参与介导E2的促细胞迁移效应。
[Abstract]:Objective to investigate the effect of 17 尾 -estradiol E _ 2 on the migration of human breast cancer cells and its signal mechanism. Methods estrogen receptor ER-positive MCF-7 and ER negative MDA-MB-468 breast cancer cells were used as the model to induce cell migration. The ability of cell migration was detected by scratch assay. The expression of silencing fibronectin (FN) gene was detected by Western blot method. The intracellular CANP activity was interfered with by Calpeptinine Calco, a specific inhibitor of calpain. Results the migration of MCF-7 and MDA-MB-468 breast cancer cells was significantly increased after 24 h treatment with E2C50 (P0.05) and P0.05 (40.78 卤4.78), respectively. FN protein expression was upregulated in MCF-7 and MDA-MB-468 breast cancer cells. P0. 05) and 1. 86 times P0. 01 mol / L ~ (-1)) could significantly inhibit the proliferation of MCF-7 and MDA-MB-468 breast cancer cells induced by E 2. The inhibition rates were 49.55 卤6. 44P 0.05) and 36. 85 卤4. 40P0.01Cal significantly inhibited the up-regulation of FN protein expression in MCF-7 and MDA-MB-468 breast cancer cells, respectively. The inhibitory rates were 80.12 卤4.55% and 78.84 卤5.70%, respectively. Silencing FN with P0.01 siRNA could inhibit the migration of MCF-7 and MDA-MB-468 breast cancer cells induced by E _ 2 (40.65 卤5.80% P 0.01) and 40.88 卤6.02% P 0.05%, respectively. The inhibitory rates were 40.65 卤5.80% and 40.88 卤6.02%, respectively, and the inhibitory rates were 40.65 卤5.80% and 40.88 卤6.02%, respectively. Conclusion E2 can promote the migration of ER positive or negative breast cancer cells, and the CANP-FN signaling pathway may play a role in promoting the migration of E 2 cells.
【作者单位】：贵州医科大学基础医学院生理学教研室;贵州医科大学基础医学院药理学教研室;
【基金】：国家自然科学基金资助项目(No 31660345,31360252)
【分类号】：R737.9

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