[1]胡芳,宋如珺,朱敏,等.葫芦巴碱调节Hippo/YAP信号通路对结直肠癌细胞增殖、迁移、侵袭及凋亡的影响[J].陕西医学杂志,2025,54(9):1155-1160.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.001]
　HU Fang,SONG Rujun,ZHU Min,et al.Effects of trigonelline on proliferation,migration,invasion and apoptosis of colorectal cancer cells by regulating Hippo/YAP signaling pathway[J].,2025,54(9):1155-1160.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.001]
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葫芦巴碱调节Hippo/YAP信号通路对结直肠癌细胞增殖、迁移、侵袭及凋亡的影响

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年9期
页码:
1155-1160
栏目:
基础研究
出版日期:
2025-09-05

文章信息/Info

Title:
Effects of trigonelline on proliferation,migration,invasion and apoptosis of colorectal cancer cells by regulating Hippo/YAP signaling pathway
作者:
胡芳1; 宋如珺1; 朱敏2; 朱惠萍3
（1.南京中医药大学附属苏州市中医医院药学部，江苏 苏州 215000；2.南京中医药大学附属江苏省中医院药学部，江苏 南京 210029；3.南京中医药大学附属苏州市中医医院脾胃科，江苏 苏州 215000）
Author(s):
HU Fang1; SONG Rujun1; ZHU Min2; ZHU Huiping3
(1.Department of Pharmacy,Suzhou TCM Hospital,Nanjing University of Chinese Medicine,Suzhou 215000,China;2.Department of Pharmacy,Jiangsu Provincial Hospital of TCM,Nanjing University of Chinese Medicine,Nanjing 210029,China;3.Department of Spleen and Stomach,Suzhou TCM Hospital,Nanjing University of Chinese Medicine,Suzhou 215000,China)
关键词:
结直肠癌; 葫芦巴碱; Hippo/YAP信号通路; 增殖; 迁移; 侵袭; 细胞凋亡
Keywords:
Colorectal cancer; Trigonelline; Hippo/YAP signaling pathway; Proliferation; Migration; Invasion; Apoptosis
分类号:
R 73-3
DOI:
DOI:10.3969/j.issn.1000-7377.2025.09.001
文献标志码:
A
摘要:
目的：研究葫芦巴碱（TRG）通过调节Hippo/Yes相关蛋白（YAP）信号通路对结直肠癌（CRC）细胞增殖、迁移、侵袭及凋亡的影响。方法：使用浓度为0、20、40、80、160、320 μmol/L的TRG处理CRC细胞（HCT116细胞）24 h后，MTT法检测细胞存活率，筛选出TRG最适浓度。将HCT116细胞分为五组：对照组（Control组）、TRG低浓度组（TRG-L组）、TRG中浓度组（TRG-M组）、TRG高浓度组（TRG-H组）和TRG-H+YAP抑制剂维替泊芬组（TRG-H+VP组），各组均处理24 h。Edu实验检测细胞增殖，细胞划痕实验检测细胞迁移，Transwell实验检测细胞侵袭，流式细胞术检测细胞凋亡，Western blot检测B细胞淋巴瘤-2蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）、大肿瘤抑制蛋白1（LATS1）、Yes相关蛋白（YAP）、磷酸化YAP(p-YAP)蛋白水平。构建CRC裸鼠移植瘤模型，检测TRG对移植瘤质量和体积的影响。结果：浓度为20~320 μmol/L的TRG均可降低HCT116细胞的存活率（均P<0.05），且呈浓度依赖性降低，IC50值为168.25 μmol/L，因此选择浓度为40、80、160 μmol/L的TRG进行后续实验。与Control组比较，TRG-L组、TRG-M组和TRG-H组HCT116细胞Edu阳性率、划痕愈合率、细胞侵袭数、Bcl-2蛋白水平显著下降，而Bax、LATS1蛋白水平、p-YAP/YAP比值和细胞凋亡率显著升高（均P<0.05）。与TRG-H组比较，TRG-H+VP组HCT116细胞Edu阳性率、划痕愈合率、细胞侵袭数、Bcl-2蛋白水平显著升高，而Bax、LATS1蛋白水平、p-YAP/YAP比值和细胞凋亡率显著下降（均P<0.05）。裸鼠移植瘤实验表明，与对照组比较，TRG组移植瘤的质量和体积显著降低（均P<0.05）。结论：TRG可能通过上调Hippo/YAP信号通路的表达，抑制HCT116细胞的增殖、迁移、侵袭，并诱导细胞凋亡。
Abstract:
Objective:To explore the impacts of trigonelline (TRG) on the proliferation,migration,invasion,and apoptosis of colorectal cancer (CRC) cells by adjusting Hippo/YAP signaling pathway.Methods：HCT116 cells were treated with TRG at concentrations of 0,20,40,80,160,320 μmol/L for 24 hours.The cell survival rate was measured by MTT assay to screen for the optimal concentration of TRG.HCT116 cells were grouped Control group,low-concentration group of TRG (TRG-L group),medium-concentration group of TRG (TRG-M group),high-concentration group of TRG (TRG-H group),and high-concentration of TRG+YAP inhibitor retinapine group (TRG-H+VP group),and each group was treated for 24 hours.Edu assay was used to detect the effect of TRG on cell proliferation in various groups.Cell scratch assay and Transwell assay were performed to detect TRG cell migration and invasion,respectively.Flow cytometry was performed to detect cell apoptosis.Western blot was performed to detect Bax,Bcl-2,LATS1,YAP and p-YAP proteins.The CRC nude mouse transplantation tumor model was constructed,and the effects of TRG on the quality and volume of the transplanted tumor ere detected.Results:TRG at concentrations of 20 to 320 μmol/L could reduce the survival rate of HCT116 cells (all P<0.05),in a concentration dependent manner,with an IC50 value of 168.25 μmol/L.Therefore,TRG at concentrations of 40,80,160 μmol/L were selected for subsequent experiments.Compared with Control group,the TRG-L group,TRG-M group and TRG-H group showed a clear decrease in the number of Edu positive rate,scratch healing rate,number of invasive cells,and Bcl-2 protein in HCT116 cells,and a clear raise in Bax,p-YAP/YAP,LATS1 proteins and apoptosis rate (all P<0.05).Compared with TRG-H group,the TRG-H+VP group showed a clear increase in the number of Edu positive rate,scratch healing rate,number of invasive cells,and Bcl-2 protein in HCT116 cells,and a clear decrease in Bax,p-YAP/YAP,LATS1 proteins,and apoptosis rate (all P<0.05).The nude mouse transplant tumor experiment found that the TRG group had clearly lower mass and volume of transplanted tumors than control group (all P<0.05).Conclusion:TRG may block the proliferation,migration,invasion and induce apoptosis of HCT116 cells by up-regulating the Hippo/YAP signaling pathway.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（81904238）；江苏省苏州市应用基础研究（医疗卫生）科技创新项目（SYWD2024340）；江苏省苏州市科技发展计划项目(SKYXD2022031)
更新日期/Last Update: 2025-09-04