目的 探究吴茱萸碱（EVO）对子宫内膜癌（EC）细胞的抗癌作用，并探讨其可能的作用机制。方法 培养EC细胞株HEC-1A、Ishikawa和AN3CA，不同浓度EVO（0、1、2、4、8 μmol/L）处理，噻唑蓝（MTT）检测EVO对不同EC细胞株增殖的影响并计算半数抑制浓度（IC50）。培养Ishikawa细胞，将其分为：Control组（不做任何处理）、EVO组（4 μmol/L EVO）、AG490组［50 μmol/L AG490，Janus激酶（JAK）抑制剂］、EVO+RO8191组（4 μmol/L EVO+20 μmol/L RO8191，JAK激动剂）。分别使用划痕实验和Transwell实验检测各组Ishikawa细胞迁移和侵袭能力；蛋白免疫印迹（Western Blot）法检测上皮-间质转化（EMT）及JAK/转录激活因子3（STAT3）/缺氧诱导因子-1α（HIF-1α）信号通路相关蛋白水平。结果 MTT结果显示，EVO对HEC-1A、Ishikawa和AN3CA细胞增殖有明显的抑制作用，且呈浓度依赖性（P<0.05）；EVO可显著抑制Ishikawa细胞的迁移和侵袭，上调上皮标志物E-钙粘附蛋白（E-cadherin）的蛋白表达，下调间质标志物E-钙粘附蛋白（N-cadherin）和波形蛋白（Vimentin）以及磷酸化JAK2（p-JAK2）、p-STAT3、HIF-1α的蛋白表达（P<0.05）。与EVO组相比，EVO+RO8191组Ishikawa细胞的划痕愈合率、侵袭率及N-cadherin、Vimentin、p-JAK2、p-STAT3、HIF-1α蛋白水平明显增高，E-cadherin蛋白水平明显降低（P<0.05）。结论 EVO通过抑制EC细胞EMT及JAK/STAT3/HIF-1α通路进而抑制细胞迁移和侵袭。

Objective To explore the anti-cancer effect of evodialine (EVO) on endometrial cancer (EC) cells, and to explore its possible mechanism of action.Methods EC cell lines HEC-1A, Ishikawa and AN3CA were cultured, and were treated with different concentrations of EVO (0, 1, 2, 4, 8 μmol/L), Thiazole Blue (MTT) was used to detect the effect of EVO on the proliferation of different EC cell lines, and calculates half maximal inhibitory concentration (IC50). Culture Ishikawa cells and divide them into: Control group (without any treatment), EVO group (8 μmol/L EVO), AG490 group [50 μmol/L AG490, Janus Kinase (JAK) inhibitor], EVO+RO8191 group (8 μmol/L EVO+20 μmol/L RO8191,JAK activator). Divided into the use of scratch test and Transwell test to detect the migration and invasion ability of each group of Ishikawa cells; Western Blot to detect epithclial-mesenchymal transition (EMT) and JAK/activator of transcription 3 (STAT3) / hypoxia inducible factor-1α (HIF-1α) signaling pathway-related protein levels.Results MTT results showed that EVO had a significant inhibitory effect on the proliferation of HEC-1A, Ishikawa and AN3CA cells, and showed a concentration-dependent (P<0.05); EVO could significantly inhibit the migration and invasion of Ishikawa cells, up-regulate the protein expression of epithelial marker E-cadherin, down-regulate the protein expression of interstitial markers N-cadherin and Vimentin, Phosphorylation -JAK2 (p-JAK2), p-STAT3, and HIF-1α (P<0.05). Compared with the EVO group, the scratch healing rate, invasion rate, and N-cadherin, Vimentin, p-JAK2, p-STAT3, and HIF-1α protein levels of Ishikawa cells in the EVO + RO8191 group were significantly increased, and the E-cadherin protein level was significantly reduced (P<0.05).Conclusion EVO inhibits cell migration and invasion by inhibiting EC cell EMT and JAK/STAT3/HIF-1α pathway.

江苏省中医药局科技项目（YB2018120）：吴茱萸碱调控EMT及JAK/STAT3/HIF-1α信号通路对子宫内膜癌作用及机制研究，负责人：张莉。