目的：探究甜橙黄酮调节Fas/FasL信号通路对子宫内膜癌细胞恶性生物学行为的影响。方法：选择人子宫内膜癌细胞Ishikawa（ISK）、RL95-2、AN3-CA及KLE为研究对象，采用CCK-8法初步检测4种细胞对甜橙黄酮的敏感性（以120 μmol/L处理48 h）。在此基础上，选择对甜橙黄酮较为敏感的ISK细胞为后续研究对象，分为对照组、L-甜橙黄酮组（40 μmol/L）、M-甜橙黄酮组（80 μmol/L）、H-甜橙黄酮组（120 μmol/L）、H-甜橙黄酮 + si-NC 组及H-甜橙黄酮 + si-Fas 组。采用CCK-8 法、克隆形成实验、Transwell实验及流式细胞术，分别检测各组细胞的增殖、侵袭和凋亡水平。采用血管形成拟态实验检测各组细胞的血管形成拟态能力，WB 法检测各组细胞中Fas、FasL 及cleaved caspase-8 蛋白的表达水平。结果：甜橙黄酮对子宫内膜癌细胞ISK、RL95-2、AN3-CA和KLE的增殖具有抑制作用（均P < 0.01），其中对ISK细胞的作用最显著。在ISK细胞中，与对照组相比，L-甜橙黄酮组、M-甜橙黄酮组、H-甜橙黄酮组的细胞增殖水平、克隆形成数、侵袭细胞数和血管形成拟态分支数均逐渐降低，而细胞凋亡率及Fas、FasL、cleaved caspase-8蛋白表达水平均逐渐升高，且浓度越高，上述指标变化幅度越明显（P < 0.01）。与H-甜橙黄酮 + si-NC组相比，H-甜橙黄酮 + si-Fas 组ISK 细胞的细胞增殖水平、克隆形成数、侵袭细胞数和血管形成拟态分支数均升高，而细胞凋亡率及Fas、FasL、cleaved caspase-8蛋白表达水平均降低（P < 0.01）。结论：甜橙黄酮抑制子宫内膜癌细胞的增殖、侵袭及血管形成拟态能力，并诱导凋亡，其机制可能与Fas/FasL信号通路的激活有关。

Objective: To investigate the effect of sinensetin on malignant biological behaviors of endometrial cancer cells through regulation of the Fas/FasL signaling pathway. Methods: Human endometrial cancer cell lines Ishikawa (ISK), RL95-2, AN3-CA, and KLE were selected as research subjects. The CCK-8 assay was initially used to screen the inhibitory effect of sinensetin on the proliferation of these four cell lines (treatment with 120 μmol/L for 48 h). Based on this, ISK cells, which were more sensitive to sinensetin, were selected for subsequent experiments and divided into the following groups: control group, L-sinensetin group (40 μmol/L), M-sinensetin group (80 μmol/L), H-sinensetin group (120 μmol/L), H-sinensetin + si-NC group, and H-sinensetin + si-Fas group. The CCK-8 assay, colony formation assay, Transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis, respectively. Vasculogenic mimicry assay was performed to assess the vasculogenic mimicry-forming ability of cells in each group, while WB was employed to detect the protein expression levels of Fas, FasL, and cleaved caspase-8 in each group. Results: Sinensetin inhibited the proliferation of endometrial cancer cell lines ISK, RL95-2, AN3-CA, and KLE (all P < 0.01), with the most pronounced effect observed in ISK cells. In ISK cells, compared with the control group, the levels of cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches in the L-sinensetin group, M-sinensetin group, and H-sinensetin group gradually decreased, while the apoptosis rate and the protein expression levels of Fas, FasL, and cleaved caspase-8 gradually increased. Moreover, higher concentrations of sinensetin were associated with more pronounced changes in the above indicators (P < 0.01). Compared with the H-sinensetin + si-NC group, the H-sinensetin + si-Fas group showed increased cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches, as well as decreased apoptosis rate and reduced protein expression levels of Fas, FasL, and cleaved caspase-8 in ISK cells (P < 0.01). Conclusion: Sinensetin inhibits proliferation, invasion, and vasculogenic mimicry of endometrial cancer cells and induces apoptosis, which may be associated with the activation of the Fas/FasL signaling pathway.

云南省科技厅科技计划项目（202101AZ070001-031）