槲皮素下调miR-146抑制甲状腺癌细胞增殖并诱导凋亡

作者：刘东杰，陈红跃，雷 震，杨萌萌，王鹏宇

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引用：引用：刘东杰，陈红跃，雷震，杨萌萌，王鹏宇.槲皮素下调miR-146抑制甲状腺癌细胞增殖并诱导凋亡[J].中医药导报,2025,31(10):16-21.

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摘要：目的：探讨槲皮素（Que）对甲状腺癌细胞增殖、凋亡的影响及潜在机制。方法：以人甲状腺乳头状癌（B-CPAP）细胞为研究对象，设置对照组和加药组，以不同浓度Que干预甲状腺癌细胞。细胞计数试剂盒-8（CCK-8）法检测细胞活力，依据结果选取低、中、高3个浓度Que用于后续实验；5-乙炔基-2'-脱氧尿苷（EdU）检测细胞增殖；倒置显微镜观察细胞形态变化；流式细胞术检测细胞凋亡及周期；Western blotting检测B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、细胞周期蛋白D1（Cyclin D1）、增殖细胞核抗原（PCNA）蛋白的相对表达；RT-qPCR法检测微小RNA-146（miR-146） mRNA的相对表达量。结果：在一定浓度范围内，与对照组比较，相同作用时间，随着Que浓度增加，细胞OD值显著降低（P<0.05），且呈浓度依赖性；不同作用时间比较，Que浓度在40、80、160 μmol/L时，细胞OD值差异更为显著，且作用24 h时，组间差异更为显著。与对照组比较，Que低浓度组（40 μmol/L）、中浓度组（80 μmol/L）和高浓度组（160 μmol/L）细胞增殖能力显著降低；Que各加药组细胞形态发生变化，随着药物浓度升高，细胞体积缩小、形态皱缩，漂浮的死亡细胞增多；Que各浓度组细胞总凋亡率均显著升高（P<0.01），随着药物浓度的升高，细胞G1期延长，S期缩短，细胞周期阻滞于G1期（P<0.05）；Que各浓度组增殖相关蛋白PCNA、周期相关蛋白CyclinD1、凋亡相关蛋白Bcl-2表达均显著降低（P<0.05）；Que加药组miR-146 mRNA相对表达量显著降低（P<0.05）。结论：Que具有抗甲状腺癌作用，能抑制B-CPAP细胞的增殖，阻滞细胞周期，促进凋亡，其作用机制可能与下调miR-146表达有关。

关键词：甲状腺癌；槲皮素；细胞凋亡；细胞增殖；微小RNA-146；人甲状腺乳头状癌细胞

Abstract：Objective: To investigate the effect of quercetin (Que) on the proliferation and apoptosis of thyroid cancer cells and its potential mechanism. Methods: Human papillary thyroid carcinoma (B-CPAP) cells were the research object, and control group and dosing group were set up. Different concentrations of Que were used to intervene thyroid carcinoma cells. Cell viability was detected by CCK-8 method, and three concentrations of Que were selected for subsequent experiments according to the results. EdU detected cell proliferation. The morphological changes of cells were observed by inverted microscope. Apoptosis and cell cycle were detected by flow cytometry. The expressions of Bax, Bcl-2, Cyclin D1 and PCNA were detected by Western blotting. RT-qPCR method was used to detect the expression of miR-146 mRNA. Results: In a certain concentration range, when the drug concentration was different, compared with the control group, with the increase of drug concentration, the cell OD value was obviously reduced (P<0.05). Compared with the same concentration and different action time, the difference of cell OD value was more significant when the drug concentration was 40, 80 and 160 μmol/L. Moreover, the difference between the groups became more significant after 24 hours of action. Compared with the control group, the cell proliferation ability of low (40 μmol/L), medium (80 μmol/L) and high (160 μmol/L) concentrations of Que was significantly reduced. Compared with the control group, the cell morphology of Que groups changed. With the increase of drug concentration, the cell volume decreased, and the shape shrank. The floating dead cells increased. The total apoptosis rate of Que cells in all groups increased significantly (P<0.01). With the increase of drug concentration, cell G1 was prolonged, and S phase was shortened. Cell cycle was arrested in G1 phase (P<0.05). The expression of proliferating protein PCNA, Cyclin D1 and Bcl-2 decreased significantly (P<0.05) in each addition group of Que. The expression of miR-146 mRNA in Que group decreased significantly (P<0.05). Conclusion: Que has anti-thyroid cancer effect, which can inhibit the proliferation of human papillary thyroid carcinoma B-CPAP cells, block cell cycle and promote apoptosis, and its mechanism may be related to down-regulating the expression of miR-146.

Key words：thyroid carcinoma; Quercetin; cell apoptosis; cell proliferation; miR-146; human papillary thyroid carcinoma cells

发布时间：2025-11-12

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