Hedgehog信号转导通路对人乳腺癌细胞MDA-MB-231侵袭转移的影响及其机制

Effect of Hedgehog Signaling Pathway on Invasion and Metastasis of Human Breast Cancer MDA-MB-231 Cells and Relevant Mechanism

目的探讨Hedgehog信号转导通路对人乳腺癌细胞MDA-MB-231侵袭转移的影响及其机制。方法应用Hedgehog信号转导通路抑制剂环巴胺(Cyclopamine)处理MDA-MB-231细胞,Transwell小室侵袭迁移实验检测细胞体外侵袭和转移能力;明胶酶谱实验检测细胞MMP-9和MMP-2的活性;Western blot法检测细胞P-c-Jun和MMP-9蛋白的表达;RT-PCR法检测细胞Gli1、c-jun和MMP-9基因mRNA的表达。结果经Cyclopamine处理后,MDA-MB-231细胞的侵袭迁移能力明显下降;MMP-9的活性降低;P-c-Jun和MMP-9蛋白表达降低;Gli1、c-jun和MMP-9基因mRNA的表达水平下降。结论 MDA-MB-231细胞存在Hedgehog信号转导通路的激活;活化的Hedgehog信号转导通路可通过上调c-jun和MMP-9的表达,促进肿瘤细胞的侵袭转移。

Objective To investigate the effect of Hedgehog signaling pathway on invasion and metastasis of human breast cancer MDA-MB-231 cells as well as the relevant mechanism.Methods MDA-MB-231 cells were treated with cyclopamine,an inhibitor of Hedgehog signaling pathway,and evaluated for invasion and metastasis abilities in vitro by Transwell test,for matrix metal protease-9（MMP-9） and MMP-2 activities by gelatin zymography,for expressions of P-c-Jun and MMP-9 proteins by Western blot,and for expressions of Glil,c-jun and MMP-9 mRNAs by RT-PCR.Results The invasion and metastasis abilities of MDA-MB-231 cells after treatment with cyclopamine decreased significantly,while MMP-9 activity,expression levels of P-c-Jun and MMP-9 proteins as well as Glil,c-jun and MMP-9 mRNAs decreased.Conclusion Hedgehog signaling pathway was activated in MDA-MB-231 cells,which promoted the invasion and metastasis of tumor cells by up-regulating the expressions of c-jun and MMP-9.