蓝萼乙素对三阴性乳腺癌MDA-MB-231细胞增殖、迁移及侵袭的影响

Effects of Glaucocalyxin B on Cell Proliferation,Migration and Invasion of Triple-negative Breast Cancer Cells

目的:探讨蓝萼乙素对三阴性乳腺癌MDA-MB-231细胞增殖、迁移及侵袭的影响及其作用机制。方法:体外培养人乳腺癌细胞MDA-MB-231,加入不同浓度(0、2、4、8μmol/L)蓝萼乙素干预处理,采用MTT法检测细胞增殖能力;划痕实验考察细胞迁移能力;Transwell小室法考察细胞侵袭能力;Western blotting法检测细胞内p38MAPK、p-p38MAPK、FOXO3a及上皮-间质转化(EMT)相关标志物(E-cadherin、Vimentin及N-cadherin)的表达水平。结果:蓝萼乙素浓度为2、4、8μmol/L时,细胞增殖率分别为(83.2±6.90)%、(70.72±6.53)%、(45.43±7.51)%,较空白对照组[(100.00±7.84)%]降低;细胞侵袭数量分别为(300.54±24.91)、(255.44±23.59)、(208.66±36.18),较空白对照组(368.44±28.32)降低;细胞迁移距离分别为(487.11±53.00)μm、(394.93±61.91)μm、(312.88±35.42)μm,较空白对照组[(559.37±75.77)μm]降低;p-p38MAPK表达量分别为(1.38±0.11)、(1.69±0.13)、(2.23±0.19),较空白对照组(1.00±0.09)增加;FOXO3α表达量分别为(1.40±0.16)、(1.97±0.31)、(2.44±0.26),较空白对照组(1.00±0.18)增加;E-cadherin表达量分别为(1.15±0.11)、(1.77±0.22)、(1.86±0.15),较空白对照组(1.00±0.11)增加;Vimentin表达量分别为(0.86±0.04)、(0.49±0.05)、(0.54±0.04),较空白对照组(1.00±0.04)减少;N-cadherin表达量分别为(0.66±0.07)、(0.58±0.08)、(0.42±0.04),较空白对照组(1.00±0.12)减少,差异均有统计学意义(P<0.05)。结论:蓝萼乙素可通过介导p38MAPK/FOXO3a信号传导有效干扰肿瘤细胞EMT进程,发挥其抑制三阴性乳腺癌细胞增殖、迁移及侵袭的作用。

Objective To investigate the effects of Glaucocalyxin B(GLB)on the proliferation,migration and invasion of MDA-MB-231 cells in triple negative breast cancer.Methods MDA-MB-231 cells were cultured in vitro and then MTT assay was used to detect cell proliferation.The cell migration ability was investigated by scratch test.Transwell assay was used to test the ability of cell invasion.Western blotting was used to analyze the expression levels of p 38 MAPK,p-p 38 MAPK,FOXO 3αand related markers of epithelial-mesenchymal transition(EMT).Results With the increase of GLB concentration(2,4 and 8μmol/L),cell proliferation rates[(83.2±6.90)%,(70.72±6.53)%and(45.43±7.51)%]were significantly decreased compared with control group[(100.00±7.84)%,P<0.05,P<0.01].The numbers of invasive cells[(300.54±24.91),(255.44±23.59)and(208.66±36.18)]were significantly decreased compared with those of the control group[(368.44±28.32),P<0.05,P<0.01].Cell migration distances[(487.11±53.00)μm,(394.93±61.91)μm and(312.88±35.42)μm]were significantly decreased compared with those of the control group[(559.37±75.77)μm,P<0.05,P<0.01].p-p38 MAPK expression[(1.38±0.11),(1.69±0.13)and(2.23±0.19)]was significantly increased compared with that of the control group[(1.00±0.09),P<0.05,P<0.01].FOXO 3αexpression[(1.40±0.16),(1.97±0.31)and(2.44±0.26)]were significantly increased compared with those of the control group[(1.00±0.18),P<0.05,P<0.01].E-cadherin expression[(1.15±0.11),(1.77±0.22)and(1.86±0.15)]was significantly increased compared with that of the control group[(1.00±0.11),P<0.05,P<0.01].Vimentin expression[(0.86±0.04),(0.49±0.05)and(0.54±0.04)]was significantly decreased compared with that of the control group[(1.00±0.04),P<0.05,P<0.01].N-cadherin expression[(0.66±0.07),(0.58±0.08)and(0.42±0.04)]was significantly decreased compared with that of the control group[(1.00±0.12),P<0.05,P<0.01].Conclusion GLB can effectively interfere with the EMT process of tumor cells by mediating p 38 MAPK/FOXO 3 a signaling pathway and it finally plays an important role in inhibiting the proliferation,migration and invasion of triple-negative breast cancer cells.