鸦胆子油对三阴性乳腺癌细胞Wnt/β-catenin通路及上皮间质转化的影响

Effects of Brucea javanica oil on Wnt/β-catenin pathway and epithelial mesenchymal transition in triple negative breast cancer cells

目的探讨鸦胆子油对三阴性乳腺癌(TNBC)细胞Wnt/β-连环蛋白(β-catenin)通路及上皮间质转化(EMT)等生物学过程的影响。方法将细胞分为对照组(仅添加培养基)、鸦胆子油组(1mg/mL鸦胆子油)和AZD2858组(1 mg/mL鸦胆子油+2μmol/L AZD2858),蛋白免疫印迹(Western blot)法检测BT-549、MDA-MB-231细胞中Wnt3a、β-catenin、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)表达情况。结果与对照组相比,鸦胆子油组BT-549、MDA-MB-231细胞凋亡率及细胞中E-cadherin蛋白表达水平显著升高(P<0.05),迁移、侵袭细胞数及细胞中Wnt3a、β-catenin、N-cadherin蛋白表达水平显著降低(P<0.05),细胞EMT形态学转变受到抑制;与鸦胆子油组相比,AZD2858组BT-549、MDA-MB-231细胞凋亡率及细胞中E-cadherin蛋白表达水平显著降低(P<0.05),迁移、侵袭细胞数及细胞中Wnt3a、β-catenin、N-cadherin蛋白表达水平显著升高(P<0.05),部分细胞发生EMT形态学转变。结论鸦胆子油可能通过抑制Wnt/β-catenin通路激活,对TNBC细胞BT-549、MDA-MB-231的增殖、迁移、侵袭、EMT过程起抑制作用,对细胞凋亡起促进作用。

Objective To investigate the effects of Brucea javanica oil on Wnt/β-catenin pathway and epithelial mesenchymal transition(EMT) in triple negative breast cancer(TNBC) cells. Methods The cells were divided into control group(only adding medium), Brucea javanica oil group(1 mg/mL Brucea javanica oil) and AZD2858 group(1 mg/mL Brucea javanica oil+2 μmol/L AZD2858), Western blot was used to detect the expression of Wnt3a, β-catenin, E-cadherin and N-cadherin in BT-549 and MDA-MB-231 cells. Results Compared with those in the control group, the apoptosis rate of BT-549 and MDA-MB-231 cells and the expression level of E-cadherin protein in BT-549 and MDA-MB-231 cells in the Brucea javanica oil group were significantly higher(P<0.05), the numbers of migration and invasion cells and the protein expression levels of Wnt3a, β-catenin and N-cadherin were significantly lower(P<0.05), cell EMT morphological changes was inhibited;compared with those in the Brucea javanica oil group, the apoptosis rate of BT-549 and MDA-MB-231 cells and the expression level of E-cadherin protein in BT-549 and MDA-MB-231 cells in AZD2858 group were significantly lower(P<0.05), the numbers of migration and invasion cells and the protein expression levels of Wnt3a, β-catenin and N-cadherin were significantly higher(P<0.05) some cell occurrence EMT morphological transformation. Conclusion Brucea javanica oil may inhibit the proliferation, migration, invasion and EMT process of TNBC cells BT-549 and MDA-MB-231 by inhibiting Wnt/β-catenin pathway activation, and then promote cell apoptosis.