丙泊酚抑制Wnt信号诱导的EMT降低乳腺癌细胞侵袭迁移能力的机制

Propofol inhibits EMT induced by Wnt signal and reduces invasion and Migration of Breast Cancer cells

目的探讨丙泊酚抑制Wnt信号诱导的EMT降低乳腺癌细胞侵袭迁移能力的机制。方法用浓度为40μmol/L的丙泊酚处理人乳腺癌MDA-MB-231细胞,Western blot检测Wnt信号相关蛋白β-catenin、cyclinDl和c-myc及EMT相关分子E-cadherin、vimentin和N-cadherin的蛋白表达。用Wnt信号抑制剂DKK-1或激活剂LiCl处理MDA-MB-231细胞,MTT法检测细胞活力,Western blot检测E-cadherin、vimentin和N-cadherin的蛋白表达。丙泊酚及丙泊酚与DKK-1或LiCl联用处理MDA-MB-231细胞,transwell小室实验检测细胞侵袭及迁移能力的变化。结果丙泊酚可下调β-catenin、cyclinDl、c-myc、vimentin和N-cadherin的蛋白表达,上调E-cadherin的蛋白表达,与对照组比较差异具有统计学意义(P<0.05)。DKK-1可抑制MDA-MB-231细胞的活力,下调vimentin和N-cadherin的蛋白表达,上调E-cadherin的蛋白表达,而LiCl可增加细胞活力,上调vimentin和N-cadherin的蛋白表达,下调E-cadherin的蛋白表达,与对照组比较差异均具有统计学意义(P<0.05)。丙泊酚可抑制MDA-MB-231细胞的侵袭及迁移能力,与对照组比较差异具有统计学意义(P<0.05),丙泊酚+DKK-1可抑制MDA-MB-231细胞的侵袭及迁移能力,而丙泊酚+LiCl可增加MDA-MB-231细胞的侵袭及迁移能力,与丙泊酚组比较差异具有统计学意义(P<0.05)。结论丙泊酚可通过抑制Wnt信号诱导的EMT降低乳腺癌细胞的侵袭迁移能力。

Objective To investigate the mechanism of propofol reducing the invasion and migration abilities of breast cancer MDA-MB-231 cells by inhibition of Wnt signaling induced EMT.Methods Human breast cancer MDAMB-231 cells were treated with propofol at 40μmol/L,and the protein expression ofβ-catenin,cyclinDl and c-myc,Ecadherin,vimentin and N-cadherin was determined by Western blot.MDA-MB-231 cells were treated with Wnt signal inhibitor DKK-1 or activator LiCl,and the cell viability was measured by MTT assay,and the protein expression of Ecadherin,vimentin and N-cadherin was determined by Western blot.MDA-MB-231 cells were treated with propofol,propofol combined with DKK-1 or LiCl,and transwell cell assays were used to detect cell invasion and migration abilities.Results Propofol down-regulated the protein expression ofβ-catenin,cyclinDl,c-myc,vimentin and N-cadherin,and up-regulate the protein expression of E-cadherin,the difference was statistically significant compared with control group(P<0.05).DKK-1 inhibited the viability of MDA-MB-231 cells,down-regulated the protein expression of vimentin and N-cadherin,up-regulated the protein expression of E-cadherin,while LiCl increased the cell viability,up-regulated the protein expression of vimentin and N-cadherin,and down-regulated the protein expression of E-cadherin,the difference was statistically significant compared with control group(P<0.05).Propofol inhibited the invasion and migration abilities of MDA-MB-231 cells,compared with control group,the difference was statistically significant(P<0.05).Propofol+DKK-1 inhibited the invasion and migration abilities of MDA-MB-231 cells,while propofol+LiCl increased the invasion and migration abilities of MDA-MB-231 cells,the difference was statistically significant compared with propofol group(P<0.05).Conclusion Propofol inhibits the invasion and migration abilities of breast cancer cells by inhibition of Wnt signaling induced EMT.