摘要目的:探讨丹皮酚(paeonol，Pae)对三阴乳腺癌细胞系MDA-MB-231细胞增殖、侵袭和上皮-间质转化(epithelial mesenchymal transition，EMT)的影响及可能机制。方法:不同浓度Pae处理MDA-MB-231细胞后，设立对照样本。采用CCK8方法检测细胞增殖活性；Transwell法检测细胞的侵袭能力；流式细胞技术检测细胞周期；Western blot检测整合素β3 (integrin β3，ITGB3)、p38丝裂原活化蛋白激酶(mitogen-activated protein kinases，p38MAPK)、磷酸化-p38MAPK(phosphorylated-p38MAPK，p-p38MAPK)蛋白的表达以及EMT相关标志物纤维连接蛋白(fibronectin，FN)、波形蛋白(vimentin，Vim)、N-钙粘蛋白(N-cadherin，N-cad)的表达变化。结果:60 mg/L的Pae对于乳腺癌细胞产生了明显的抑制作用，故本实验使用60 mg/L的Pae浓度。Pae分别处理24、48 h后，G0/G1的细胞周期分别从对照组的50.6%增加到53.0%和65.4%。S期处理48 h后，Pae组肿瘤细胞百分比从37.6%降低至26.6%。Transwell结果显示，与对照组相比，Pae处理乳腺癌细胞24、48 h后细胞侵袭数明显减少，差异有统计学意义[个：(378.73±47.62)比(193.64±32.54)或(174.37±27.83)， t＝5.35、5.75， P值均<0.05]。与对照组相比，Pae处理后乳腺癌细胞ITGB3、p38MAPK、p-p38MAPK表达水平明显降低；EMT标记物FN、N-cad、Vim表达均显著下降，差异有统计学意义[(0.97±0.19)比(0.48±0.10)，(1.24±0.24)比(0.56±0.18)，(0.93±0.18)比(0.51±0.13)， t＝4.08、3.93、3.28， P值均<0.05；(0.88±0.16)比(0.46±0.08)，(0.96±0.17)比(0.43±0.12)，(0.87±0.15)比(0.37±0.13)， t＝4.06、4.42、4.36， P值均<0.05]。 结论:Pae显著抑制三阴乳腺癌细胞系MDA-MB-231细胞增殖，侵袭和EMT，该作用可能与ITGB3/p38MAPK信号通路激活有关。

abstractsObjective:To explore the effect of paeonol(Pae) on the expansion, invasion and epithelial-mesenchymal transition (EMT) of triple negative breast cancer cell line MDA-MB-231 and its possible mechanism.Methods:After MDA-MB-231 cells were treated with Pae at different concentrations, control samples were set up. The proliferation activity was detected by CCK8 method. Transwell method was used to detect the invasiveness of cells. Flow cytometry was used to analyze the cell cycle. Western blot was used to detect the expression of integrin β3 (ITGB3), p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK(p-p38MAPK) protein, and the expression changes of EMT related markers fibronectin (FN), vimentin (Vim), and N-cadherin (N-cad).Results:The 60 mg/L Pae has obvious inhibitory effect on breast cancer cells, so 60 mg/L Pae concentration was used in this experiment. After 24 h and 48 h of treatment with Pae, the cell cycle of G0/G1 increased from 50.6% in the control group to 53.0% and 65.4% respectively. The percentage of tumor cells in the Pae group decreased from 37.6% to 26.6% after 48 h treatment in the S phase. Transwell results showed that compared with the control group, the number of cell invasion of breast cancer cells after Pae treatment for 24 h and 48 h was significantly reduced [pcs: (378.73±47.62) vs (193.64±32.54) or (174.37±27.83), t=5.35, 5.75, both P values <0.05]. Compared with the control group, the expression levels of ITGB3, p38MAPK, p-p38MAPK in breast cancer cells after Pae treatment were significantly reduced, and the expression levels of EMT markers FN, N-cad, Vim were significantly reduced[(0.97±0.19) vs(0.48±0.10), (1.24±0.24) vs(0.56±0.18), (0.93±0.18) vs(0. 51±0.13), t=4.08, 3.93, 3.28, all P values<0.05; (0.88±0.16) vs(0.46±0.08), (0.96±0.17) vs(0.43±0.12), (0.87±0.15) vs(0.37±0.13), t=4.06, 4.42, 4.36, all P values<0.05]. Conclusion:Pae can significantly inhibit the proliferation, invasion and EMT in breast cancer cells, which may be related to ITGB3/p38MAPK signal pathway activation.