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中华普通外科学文献简介:中华普通外科学文献简介,中华普通外科学文献简介[详细]

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主管:
中华人民共和国国家卫生健康委员会
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中华医学会
承办:
中山大学附属第一医院
中山大学附属中山医院
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国际刊号: 1674-0793
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首页 > 期刊列表 > FOXC2介导Hedgehog/Gli信号通路对乳腺癌侵袭及迁移的影响
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标题: FOXC2介导Hedgehog/Gli信号通路对乳腺癌侵袭及迁移的影响
摘要:

目的:探讨FOXC2介导Hedgehog/Gli信号通路通过调控上皮间质转化(EMT)途径参与乳腺癌侵袭及迁移的机制。方法:应用不同浓度环靶明(Cyclopamine)处理乳腺癌MDA-MB-231细胞,MTT法检测细胞增殖抑制率及计算药物半数抑制浓度(IC50);采用Cyclopamine或沉默FOXC2基因表达以阻断Hedgehog/Gli信号通路活化;通过Transwell小室体外侵袭实验及划痕实验分别检测阻断Hedgehog/Gli信号通路对MDA-MB-231细胞侵袭及迁移影响;Western blotting检测阻断前后Hedgehog/Gli信号通路分子Smoothened(Smo)、Gli1和EMT相关标志物FOXC2,E-cadherin及Vimentin蛋白表达变化。结果:与空白对照组比较,Cyclopamine可显著地抑制MDA-MB-231细胞增殖并呈现时效-量效关系,48 h的IC50为25 μmol/L。Transwell小室体外侵袭实验及划痕实验均显示,与未转染组及Control-siRNA组相比,FOXC2-siRNA组和Cyclopamine组细胞穿膜数及迁移率均显著降低,差异有统计学意义(P<0.05)。Western blotting显示,与未转染组及Control-siRNA组相比较,FOXC2-siRNA组及Cyclopamine组Smo、Gli1及FOXC2蛋白表达显著降低,差异有统计学意义(P<0.05)。而沉默FOXC2表达可显著降低Vimentin蛋白表达及增加E-cadherin蛋白表达,差异有统计学意义(P<0.05)。结论:FOXC2通过介导Hedgehog/Gli信号通路从而调控EMT促进乳腺癌侵袭及迁移,提示阻断该信号通路有望成为乳腺癌靶向治疗新线索。

英文摘要: Objective:To explore the mechanism of FOXC2 mediated Hedgehog/Gli signaling pathway involved in breast cancer invasion and migration by regulating epithelium mesenchymal transformation (EMT). Methods:Breast cancer MDA-MB-231 cells were treated with different concentrations Cyclopamine-a Hedgehog/Gli signaling pathway inhibitor. MTT method was used to detect the cell proliferation inhibition rate and calculated the drug half inhibitory concentration (IC50). Cyclopamine or silencing FOXC2 expression by RNA interference (siRNA) was used to block the Hedgehog/Gli signaling pathway activation. Transwell chamber invasion assay and scratch assay were used to detect invasion and migration ability of MDA-MB-231 cells after blocking Hedgehog/Gli signal pathway respectively. Western blotting was used to detect the expression of Hedgehog/Gli signaling pathway molecules Smoothened (Smo), Gli1 and EMT-related markers E-cadherin and Vimentin protein before and after blocking Hedgehog/Gli signaling pathway. Results:Compared with the blank control group, Cyclopamine could significantly inhibit the MDA-MB-231 cells proliferation and showed a time-dose effect relationship. The half inhibition inhibitory concentration was 25 μmol/L after 48 hour. Transwell chamber invasion assay and wound healing assay showed that FOXC2-siRNA group and Cyclopamine group penetrating cells and migration rates were significantly lower, as compared with the untransfected group and Control-siRNA group. The difference was statistically significant (P<0.05). Western blotting results also showed that the expression of Smo, Gli1 and FOXC2 protein was significantly decreased in FOXC2-siRNA group and Cyclopamine group, as compared with the untransfected group and Control-siRNA group (P<0.05). The expression of Vimentin protein was significantly decreased and the expression of E-cadherin protein was increased when silencing FOXC2 expression, the differences were statistically significant (P<0.05). Conclusions:FOXC2 mediates Hedgehog/Gli signaling pathway involved in breast cancer invasion and migration by regulating EMT. It is suggested that blocking the Hedgehog/Gli signal pathway may be a new targeted therapy of breast cancer.
作者:

屈洪波1;罗迪贤2;段丽丽2;胡雄强1;吴诚义3

作者单位: 郴州市第一人民医院乳腺甲状腺外科1; 郴州市第一人民医院转化医学研究所2;重庆医科大学附属第一医院内分泌乳腺外科3
期刊: 中华普通外科学文献(电子版)
年.卷(期):页码 2020 .14(5):326-330
中图分类号:
文章编号:
引用格式: [1]屈洪波1;罗迪贤2;段丽丽2;胡雄强1;吴诚义3.FOXC2介导Hedgehog/Gli信号通路对乳腺癌侵袭及迁移的影响[J/CD].中华普通外科学文献(电子版),2020,14(5):326-330 .
关键词: FOXC2;Hedgehog/Gli信号通路;上皮间质转化;乳腺肿瘤;侵袭迁移
英文关键词: FOXC2; Hedgehog/Gli signal pathway; Epithelial-mesenchymal transition; Breast tumor; Invasion and metastasis

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