[摘 要] 目的：探讨圣草次苷对食管癌KYSE30细胞增殖的影响，并基于铁死亡探讨其可能的作用机制。方法：将食管癌 KYSE30细胞分为8组：对照组（常规培养）、RSL3组（用3 μmol/L铁死亡诱导剂RSL3处理）、圣草次苷组（用75 μmol/L圣草次苷 处理）、圣草次苷 + Fer-1组（用5 μmol/L铁死亡抑制剂Fer-1 + 75 μmol/L圣草次苷处理）、Fer-1组（用5 μmol/L Fer-1处理）、oe-NC 组（转染空白载体对照）、oe-STAT3组（转染STAT3过表达载体）、oe-STAT3 + 圣草次苷组（转染STAT3过表达载体后，用75 μmol/L 圣草次苷处理）。采用CCK-8法、EdU掺入实验和克隆形成实验分别检测各组细胞的增殖能力，ELISA检测细胞内铁死亡相关指 标的水平，WB法检测STAT3/GPX4通路相关蛋白的表达。构建KYSE30细胞裸鼠皮下移植瘤模型，观察圣草次苷及Fer-1对移 植瘤生长的影响。结果：圣草次苷能够抑制KYSE30细胞增殖和克隆形成，增加活性氧（ROS）、丙二醛（MDA）、Fe2+水平，降低谷 胱甘肽（GSH）水平（均P < 0.05），并抑制裸鼠移植瘤的生长，这些作用能够被Fer-1所逆转（P < 0.05）。STAT3过表达可消除圣草 次苷对铁死亡的诱导效应及其对STAT3/GPX4通路的抑制作用（P < 0.05）。结论：圣草次苷能够通过抑制STAT3/GPX4信号通 路来诱导食管癌KYSE30细胞铁死亡，从而在食管癌中发挥显著的抗肿瘤效应。

[Abstract] Objective: To investigate the effect of Eriocitrin on the proliferation of esophageal cancer KYSE30 cells, and to explore its possible mechanism based on ferroptosis. Methods: Esophageal cancer KYSE30 cells were divided into 8 groups: the control group (conventional culture), RSL3 group (treated with 3 μmol/L ferroptosis inducer RSL3), Eriocitrin group (treated with 75 μmol/L Eriocitrin), Eriocitrin + Fer-1 group (treated with 5 μmol/L of ferroptosis inhibitor Fer-1 and 75 μmol/L Eriocitrin), Fer-1 group (treated with 5 μmol/L Fer-1 treatment), oe-NC group (transfected with blank vector control), oe-STAT3 group (transfected with STAT3 overexpression vector) and oe-STAT3 + Eriocitrin group (transfected with STAT3 overexpression vector and then treated with 75 μmol/L Eriocitrin). Proliferation abilities of cells in each group were detected using CCK-8 assay, EdU incorporation assay and clone formation assay respectively. The levels of intracellular ferroptosis-related indicators were detected using the ELISA kits. Western blotting was used to detect the expression of STAT3/GPX4 pathway-related proteins. KYSE30 cell nude mouse subcutaneous transplanted tumor model was constructed to observe the effects of Eriocitrin and Fer-1 on the growth of transplanted tumors. Results: Eriodictyol could inhibit the proliferation and clone formation of KYSE30 cells, increase the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and Fe2+, decrease the level of glutathione (GSH) (all P < 0.05) and suppress the growth of transplanted tumors in nude mice. These effects could be reversed by Fer-1 (P < 0.05). Overexpression of STAT3 could abolish the inductive effect of eriodictyol on ferroptosis and its inhibitory effect on the STAT3/GPX4 pathway (P < 0.05). Conclusion: Eriocitrin could induce ferroptosis in esophageal cancer KYSE30 cells by inhibiting STAT3/GPX4 signaling pathway and exert significant antitumor effects in esophageal cancer.

河北省自然科学基金（No. H2022206546）