[摘 要] 目的：探究芒柄花素调节JAK2/STAT3信号通路对胆囊癌细胞GBC-SD恶性生物学行为及血管生成的影响。方法： 常规培养GBC-SD细胞并构建其移植瘤裸鼠，将GBC-SD细胞和其移植瘤裸鼠分为对照组、芒柄花素组、colivelin（JAK2/STAT3 激活剂）组、芒柄花素 + colivelin组。用MTT法、Transwell实验和流式细胞术分别检测各组细胞的增殖、迁移和侵袭能力，以及凋 亡，用ELISA法检测各组细胞血管内皮生长因子（VEGF）分泌水平，血管生成拟态（VM）形成实验检测各组细胞的成管腔能力， 移植瘤实验检测芒柄花素对移植瘤生长的影响，免疫组化法检测各组移植瘤组织中CD31和VEGF表达，WB法检测各组细胞和 移植瘤组织中JAK2/STAT3通路的磷酸化水平。结果：芒柄花素可明显抑制GBC-SD细胞的增殖、迁移和侵袭能力，促进其凋亡 （均P < 0.05），抑制GBC-SD细胞分泌VEGF和VM形成（均P < 0.05），抑制GBC-SD细胞移植瘤的生长及血管生成（均P < 0.05）， 抑制移植瘤组织中VEGF表达，抑制GBC-SD细胞和其移植瘤组织中JAK2/STAT3通路的磷酸化，colivelin均可逆转芒柄花素的 上述作用（均P < 0.05）。结论：芒柄花素通过抑制JAK2/STAT3信号通路抑制GBC-SD细胞增殖、迁移、侵袭、血管形成，促进其 凋亡，JAK2/STAT3信号通路是胆囊癌临床治疗的潜在靶点。

[Abstract] Objective: To investigate the effects of formononetin on the malignant biological behavior and angiogenesis of gallbladder cancer GBC-SD cells through regulation of the JAK2/STAT3 signaling pathway. Methods: GBC-SD cells were cultured routinely, and their xenograft nude mouse models were constructed. The cells and mice were divided into control group, formononetin group, colivelin (JAK2/STAT3 activator) group, and formononetin + colivelin group. Cell proliferation, migration and invasion, and apoptosis were assessed using MTT, Transwell, and flow cytometry assays, respectively. ELISA was applied to measure the secretion levels of vascular endothelial growth factor (VEGF) in cells of each group. Vasculogenic mimicry (VM) formation assay was used to detect the tube formation ability of each group of cells. In vivo, the effects of formononetin on xenograft tumor growth were examined, and CD31 and VEGF expression in xenograft tissues were detected by immunohistochemistry. Western blotting was applied to analyze JAK2/ STAT3 phosphorylation levels in both cells and tumor tissues. Results: Formononetin significantly inhibited the proliferation, migration, and invasion of GBC-SD cells and promoted apoptosis (all P < 0.05). It also suppressed VEGF secretion and VM formation in GBC-SD cells (all P < 0.05), inhibited the growth and vascular formation of GBC-SD xenograft tumors (all P < 0.05), reduced VEGF expression in transplanted tumor tissues, and decreased phosphorylation of the JAK2/STAT3 pathway in both GBC-SD cells and their xenograft tissues. These effects of formononetin were partially reversed by colivelin (all P < 0.05). Conclusion: Formononetin inhibits GBC-SD cell proliferation, migration, invasion, and angiogenesis, and promotes apoptosis by suppressing the JAK2/STAT3 signaling pathway. The JAK2/STAT3 signaling pathway may serve as a potential therapeutic target for gallbladder cancer.

[基金项目] 张家港科技计划项目（No.202202）