双氢青蒿素作用于乳腺癌细胞抑制EMT和转移的作用及机制

Effect and mechanism of Dihydroartemisinin on EMT and metastasis of breast cancer cells

目的探讨双氢青蒿素对乳腺癌细胞上皮细胞间充质化(EMT)和转移的抑制作用及机制。方法用0μmol/L、10μmol/L、20μmol/L、40μmol/L、80μmol/L的双氢青蒿素作用于乳腺癌细胞,培养48 h后,噻唑蓝(MTT)检测细胞增殖,细胞划痕实验检测细胞迁移能力,Western blot检测细胞中钙黏蛋白E(E-cadherin)、波形蛋白(Vimentin)、蛋白激酶B(Akt)、磷酸化蛋白激酶B(p-Akt)、基质金属蛋白酶-2(MMP-2)水平。结果 10μmol/L、20μmol/L、40μmol/L、80μmol/L的双氢青蒿素作用后的乳腺癌细胞存活率、迁移率与0μmol/L双氢青蒿素作用组相比明显降低(P<0.05),80μmol/L双氢青蒿素作用组细胞存活率和迁移率最低,后续选用80μmol/L双氢青蒿素继续研究。80μmol/L双氢青蒿素作用组细胞中的Vimentin、p-Akt、MMP-2蛋白表达水平与0μmol/L双氢青蒿素作用组相比也明显降低,而细胞中E-cadherin水平升高(P<0.05)。结论双氢青蒿素能够抑制乳腺癌细胞EMT和转移,作用机制可能与Akt信号通路有关。

Objective To discuss the effect and mechanism of Dihydroartemisinin on metastasis and EMT of breast cancer cells.Methods 0 μmol/L,10 μmol/L,20 μmol/L,40 μmol/L,80 μmol/L of dihydroartemisinin were used in breast cancer cells.After culturing 48 h,cell proliferation was detected by MTT,cell scratch assay was used to detect the ability of cell migration,the levels of E-cadherin,Vimentin,Akt,p-Akt and MMP-2 in the cells were detected by Western blot.Results After the application of 10 μmol/L,20 μmol/L,40 μmol/L,80 μmol/L of dihydroartemisinin,the survival rate and migration rate of breast cancer cells were significantly lower than those of the 0 μmol/L dihydroartemisinin group （P＆lt;0.05）,the survival rate and migration rate of the 80 μmol/L of dihydroartemisinin group were the lowest.Then,follow up study adopt 80 μmol/L of dihydroartemisinin.The expression levels of Vimentin,p-Akt and MMP-2 in the 80 μmol/L dihydroartemisinin group were significantly lower than those of the 0 μmol/L dihydroartemisinin group,but the level of E-cadherin increased （P＆lt;0.05）.Conclusion Dihydroartemisinin can inhibit EMT and metastasis of breast cancer cells.The mechanism of action may be related to Akt signaling pathway.