| 叶浩,易晓雷,李旭辉,等.知母皂苷 AⅢ介导 Wnt/β-catenin信号通路增强胃癌细胞对程序性细胞死亡蛋白 -1抑制剂的敏感性[J].安徽医药,2026,30(3):492-496. |
| 知母皂苷 AⅢ介导 Wnt/β-catenin信号通路增强胃癌细胞对程序性细胞死亡蛋白 -1抑制剂的敏感性 |
| Timosaponin AⅢ-mediated Wnt/β-catenin signaling pathway to enhance the sensitivity of gastric cancer cells to programmed cell death protien-1 inhibitors |
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| DOI：10.3969/j.issn.1009-6469.2026.03.013 |
| 中文关键词: 知母属 胃癌 Wnt/β-联蛋白信号通路 程序性细胞死亡蛋白 -1 替雷利珠单抗 药物敏感性 |
| 英文关键词: Anemarrhena Gastric cancer Wnt/β-catenin signaling pathway Programmed cell death protein-1 Tirellizumab Drug sensitivity |
| 基金项目:湖南省自然科学基金项目( 2024JJ7650) |
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| 中文摘要: |
| 目的分析知母皂苷 AⅢ介导 Wnt/β-联蛋白( β-catenin)信号通路增强胃癌细胞对程序性细胞死亡蛋白 -1(PD-1)抑制剂替雷利珠单抗的敏感性。方法 2024年 2—10月，取 MKN-45系人胃癌细胞，以细胞计数试剂盒( CCK-8)法测定细胞增殖情况及半数抑制浓度( IC50)设定对照组、知母皂苷 AⅢ作用组( AⅢ组)、替雷利珠单抗作用组(单抗组)以及知母皂苷 AⅢ+替雷利珠单抗作用组( AⅢ+单抗，组)。以流式细胞术检测细胞凋亡情况，细胞划痕实验及 Transwell实验检测细胞迁移、侵袭能力，实时荧光定量逆转录聚合酶链反应( qRT-PCR)检测 β-catenin mRNA的表达水平，蛋白质印迹法检测 β-catenin蛋白的表达水平。结果 CCK-8法检测结果显示，随着知母皂苷 AⅢ与替雷利珠单抗药物浓度的升高，胃癌细胞增殖率逐渐降低(均 P<0.001)，且知母皂苷 AⅢ+替雷利珠单抗联合作用后，胃癌细胞增殖率明显低于两者的单独应用(均 P<0.001)；流式细胞检测结果显示， AⅢ+单抗组胃癌细胞凋亡率( 37.76±3.19)%明显高于对照组( 6.37±0.36)%、AⅢ组( 18.38±2.64)%与单抗组( 24.09±2.77)%(均 P<0.001)；细胞划痕实验及 Transwell实验结果显示， AⅢ+单抗组细胞迁移、侵袭能力明显弱于对照组、 AⅢ组与单抗组(均 P<0.001)； qRT-PCR检测结果显示， AⅢ+单抗组 β-catenin mRNA的表达水平明显低于对照组、 AⅢ组与单抗组(均 P<0.001)；蛋白质印迹法检测结果显示， AⅢ+单抗组 β-catenin蛋白的表达水平明显低于对照组、 AⅢ组与单抗组(均 P<0.001)。结论知母皂苷 AⅢ能够明显提升 PD-1抑制剂替雷利珠单抗对胃癌细胞的药物敏感性，促进胃癌细胞凋亡，且其作用机制可能与其能够下调 Wnt/β-catenin信号通路有关。 |
| 英文摘要: |
| Objective To study the susceptibility of gastric cancer cells to programmed cell death protein-1 (PD-1) inhibitor tirelli. zumab by means of Wnt/β-catenin signaling mediated by Timosaponin AⅢ.Methods From February to October 2024, MKN-45 hu. man gastric cancer cells were taken and measured by cell Counting Kit-8 (CCK-8) for cell proliferation and half inhibitory concentra. tion (IC50). Control group, Timosaponin AⅢ treatment group (AⅢ treatment group), tirelizumab treatment group (mAb group) and Timo.saponin AⅢ+tirelizumab treatment group (AⅢ+mAb group) were set, and cell apoptosis was detected by flow cytometry. Cell migrationand invasion ability were detected by cell scratch assay and Transwell assay. The expression level of β-catenin mRNA was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the expression level of β-catenin protein was de. tected by Western blotting.Results The results of CCK-8 assay showed that the proliferation rate of gastric cancer cells gradually de.creased with the increase of the concentration of Timosaponin AⅢ and tirellizumab (both P<0.001), and the proliferation rate of gastriccancer cells after the combined use of Timosaponin AⅢ and tirellizumab was significantly lower than that with either one used alone(both P<0.001). Flow cytometry results showed that the apoptosis rate of gastric cancer cells in AⅢ+mAb group was significantly high.er than that in control group, A Ⅲ group or mAb group [(37.76±3.19)% vs. (6.37±0.36)% , (18.38±2.64)% , (24.09±2.77)% ] (all P< 0.001). The results of cell scratch assay and Transwell assay showed that the cell migration and invasion ability of AⅢ+mAb group wassignificantly lower than that of control group, AⅢ group or mAb group (all P<0.001). qRT-PCR results showed that the expression level of β-catenin mRNA in AⅢ+mAb group was significantly lower than that in control group, AⅢ group and mAb group (all P<0.001). Western blotting analysis results showed that the expression level of β-catenin protein in AⅢ+mAb group was significantly lower than that in control group, AⅢ group and mAb group (all P<0.001).Conclusion Timosaponin AⅢ can significantly enhance the drug sen. sitivity of PD-1 inhibitor (tirelizumab) to gastric cancer cells and promote apoptosis of gastric cancer cells, whose mechanism of actionmay be related to the down-regulation of Wnt/β-catenin signaling pathway. |
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