熊果酸调节Wnt/β-catenin信号通路对甲状腺癌细胞增殖、凋亡、侵袭和迁移的影响

doi:10.11904/j.issn.1002-3070.2026.01.004

摘要/Abstract

摘要： 目的本研究旨在探讨熊果酸(ursolic acid,UA)能否通过调节Wnt/β-catenin信号通路抑制甲状腺癌细胞恶性生物学行为。方法将人甲状腺癌细胞系SW579细胞分为对照组(以DMSO处理作为空白对照)、低剂量UA组(2.5 μM UA)、高剂量UA组(5 μM UA)和高剂量UA+Wnt激动剂组(5 μM UA+0.3 μM Compound 3f);采用CCK-8法检测UA(0~10 μM)对SW579细胞增殖的影响;采用克隆形成实验检测细胞增殖能力;采用流式细胞术检测细胞凋亡;采用细胞划痕实验检测细胞迁移能力;采用Transwell实验检测细胞侵袭能力;采用Western blot检测Wnt1、β-catenin、B细胞白血病/淋巴瘤-2(B-cell leukemia/lymphoma 2,BCL2)、BCL2相关X蛋白(Bax)表达水平。结果与0 μM组相比,UA处理对SW579细胞增殖的抑制作用随浓度增加逐渐升高(P＜0.05),UA抑制SW579细胞增殖的IC₅₀为5.22 μM;与对照组相比,低剂量UA组、高剂量UA组中SW579细胞克隆形成率、划痕愈合率、细胞侵袭数以及BCL2、Wnt1和β-catenin蛋白表达水平均显著降低,细胞凋亡率和Bax蛋白表达显著升高(P＜0.05);与高剂量UA组相比,高剂量UA+Wnt激动剂组中SW579细胞克隆形成率、划痕愈合率、细胞侵袭数以及BCL2、Wnt1和β-catenin蛋白表达水平均显著升高,细胞凋亡率和Bax蛋白表达显著降低(P＜0.05)。结论 UA可能通过下调Wnt1和β-catenin水平调控Wnt/β-catenin轴,抑制人甲状腺癌细胞增殖、侵袭、迁移并诱导其凋亡。

关键词: 熊果酸, Wnt/β-联蛋白信号通路, 甲状腺癌, 增殖, 凋亡, 迁移, 侵袭

Abstract: Objective This study aimed to investigate whether ursolic acid(UA)could inhibit the malignant biological behaviors of thyroid cancer cells by regulating the Wnt/β-catenin pathway. Methods Human thyroid cancer SW579 cells were divided into four groups:the control group(treated with DMSO as a blank control),the low-dose UA group(2.5 μmol/L UA),the high-dose UA group(5 μmol/L UA),and the high-dose UA+Wnt agonist group(5 μmol/L UA + 0.3 μmol/L Compound 3f).The CCK-8 assay was used to detect the effect of UA(0-10 μmol/L)on the proliferation of SW579 cells;The colony formation assay was performed to evaluate the proliferative capacity of SW579 cells;Flow cytometry was used to detect apoptosis of SW579 cells;The cell scratch assay was conducted to assess migration ability of SW579 cells;The Transwell assay was performed to determine invasive capacity of SW579 cells;Western blot was employed to detect the protein expression of Wnt1,β-catenin,B-cell leukemia/lymphoma 2(BCL2),and BCL2-associated X protein(Bax)in SW579 cells. Results Compared with the 0 μmol/L group,UA treatment gradually enhanced the inhibitory effect on the proliferation of SW579 cells with increasing concentration(P＜0.05),and the half maximal inhibitory concentration(IC₅₀)for UA to inhibit SW579 cell proliferation was 5.22 μmol/L.Compared with the control group,UA in the low-dose and high-dose UA groups significantly reduced the colony formation rate,scratch healing rate,and number of invasive cells as well as decreased the protein expression of BCL2,Wnt1 and β-catenin in SW579 cells,while the apoptotic rate and the protein expression of Bax were significantly increased(P＜0.05).Compared with the high-dose UA group,the high-dose UA + Wnt agonist group exhibited significantly elevated the colony formation rate,scratch healing rate,number of invasive cells,and increased the protein expression of BCL2,Wnt1 and β-catenin,whereas the apoptotic rate and Bax protein expression were significantly decreased(P＜0.05). Conclusion UA may regulate the Wnt/β-catenin pathway by down-regulating the expression of Wnt1 and β-catenin,thereby inhibiting the proliferation,migration and invasion of human thyroid cancer cells and inducing apoptosis.

Key words: ursolic acid, Wnt/β-catenin pathway, thyroid cancer, proliferation, apoptosis, migration, invasion

中图分类号:

R285.5

徐静, 郭竹英, 何苗, 周文辉, 刘斌. 熊果酸调节Wnt/β-catenin信号通路对甲状腺癌细胞增殖、凋亡、侵袭和迁移的影响[J]. 实用肿瘤学杂志, 2026, 40(1): 22-29.

XU Jing, GUO Zhuying, HE Miao, ZHOU Wenhui, LIU Bin. The effects of ursolic acid on the proliferation,apoptosis,invasion,and migration of thyroid cancer cells by regulating the Wnt/β-catenin pathway[J]. Journal of Practical Oncology, 2026, 40(1): 22-29.

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