目的 探究光甘草定（GLA）对食管癌细胞增殖、凋亡、侵袭、迁移的影响并分析其是否与调节Janus蛋白酪氨酸激酶2（JAK2）/信号转导和转录激活因子3（STAT3）通路有关。方法 MTT法检测0、10、20、40、80、160、320 μmol·L^-1GLA对人食管癌细胞KYSE150存活率的影响，并计算半数抑制浓度（IC₅₀）。确定80、40、20 μmol·L^-1为后续实验GLA浓度，并设置对照组、GLA（80 μmol·L^-1）＋Colivelin（0.5 μmol·L^-1，JAK2/STAT3通路激活剂）组、GLA（80 μmol·L^-1）＋baricitini （10 μmol·L^-1，JAK2抑制剂）组，CCK8法检测细胞活力，集落形成实验检测细胞克隆能力，流式细胞仪检测细胞凋亡，Transwell实验检测细胞侵袭，伤口愈合实验检测细胞迁移，Westren blotting法检测JAK2/STAT3通路及增殖、迁移蛋白表达。建立食管癌裸鼠模型，随机分为模型组和GLA（50 mg·kg^-1）组，每天ig给药1次，治疗3周后处死小鼠，分析肿瘤质量、体积，免疫组化染色分析组织中JAK2、STAT3阳性表达。结果 与对照组比较，GLA组凋亡率显著升高（P＜0.05），细胞活力、细胞克隆数、侵袭数、迁移率显著降低（P＜0.05）。与GLA 80 μmol·L^-1组比较，GLA＋Colivelin组凋亡率显著降低（P＜0.05），细胞活力、细胞克隆数、侵袭数、迁移率显著升高（P＜0.05）；GLA＋baricitini组细胞凋亡率显著升高（P＜0.05），活力、细胞克隆数、侵袭数、迁移率显著降低（P＜0.05）。与对照组比较，GLA组细胞Bax蛋白表达显著升高（P＜0.05），p-JAK2、p-STAT3、c-MYC、Ki67、基质金属蛋白酶9 （MMP-9）表达显著降低（P＜0.05）。与GLA 80 μmol·L^-1组比较，GLA＋Colivelin组Bax蛋白表达显著降低（P＜0.05），p-JAK2、p-STAT3、c-MYC、Ki67、MMP-9蛋白表达显著升高（P＜0.05）；GLA＋baricitini组Bax蛋白表达显著升高（P＜0.05），p-JAK2、p-STAT3、c-MYC、Ki67、MMP-9蛋白表达显著降低（P＜0.05）。与模型组裸鼠比较，GLA组肿瘤质量和体积显著降低（P＜0.05），JAK2、STAT3阳性表达率显著降低（P＜0.05）。结论 GLA可能抑制JAK2/STAT3通路，进而抑制食管癌细胞增殖、侵袭、迁移，并促进凋亡。

Objective To investigate the effects of glabridin (GLA) on the proliferation, apoptosis, invasion, and migration of esophageal cancer cells and analyze whether it is related to the regulation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. Methods MTT assay was used to detect the cell survival rates of GLA intervention at 0, 10, 20, 40, 80, 160, and 320 μmol·L^-1, and IC₅₀ was calculated. 80, 40, and 20 μmol·L^-1 were determined as the doses for subsequent experiments in the GLA group, and control group, GLA (80 μmol·L^-1)+Colivelin (0.5 μmol·L^-1, JAK2/STAT3 pathway activator) group, GLA (80 μmol·L^-1) +baricitini (10 μmol·L^-1, JAK2 inhibitor) group were set up. CCK8 method was applied to detect cell viability, colony formation experiment was applied to detect cell cloning ability, transwell experiment was applied to detect cell invasion, the wound healing experiment was applied to detect cell migration, and immunoblotting was applied to detect the JAK2/STAT3 pathway and the expression of proliferation and migration proteins. A nude mouse model of esophageal cancer was established and randomly separated into a model group and a GLA (50 mg·kg^-1) group. Administer ig once a day, euthanize mice after three weeks of treatment, analyze tumor mass and volume, and perform immunohistochemical staining to analyze JAK2 and STAT3 positive expression in tissues. Results Compared with the control group, the apoptosis rate of the GLA group increased, while the cell viability, cell clone number, invasion number, and migration rate decreased (P < 0.05). Compared with the GLA 80 μmol·L^-1 group, the cell viability, number of cell clones, number of invasions, and migration rate in GLA+Colivelin group increased, while the apoptosis rate decreased (P < 0.05), the apoptosis rate of cells in the GLA+baricitinib group increased, while the vitality, number of cell clones, number of invasions, and migration rate decreased (P < 0.05). Compared with control group, the expression of Bax in cells of the GLA group increased, while the expression of p-JAK2, p-STAT3, c-MYC, Ki67, and MMP-9 decreased (P < 0.05). Compared with the GLA 80 μmol·L^-1 group, the expression of p-JAK2, p-STAT3, c-MYC, Ki67, and MMP-9 in the GLA+Colivelin group increased, while the expression of Bax decreased (P < 0.05); the expression of Bax in the GLA+ baricitinib group increased, while the expression of p-JAK2, p-STAT3, c-MYC, Ki67, and MMP-9 decreased (P < 0.05). Compared with the nude mice in model group, the tumor mass and volume in the GLA group decreased (P < 0.05), and the positive expression rates of JAK2 and STAT3 in the GLA group decreased (P < 0.05). Conclusion GLA can inhibit the JAK2/STAT3 pathway, thereby inhibiting the proliferation, invasion, migration, and promoting apoptosis of esophageal cancer cells.

R285.5

河南省教育科学“十四五”规划项目（2021YB0515）