| 郭贻龙,陈宝,黎伟.抗氧化反应元件信号通路调控胆囊癌细胞增殖、侵袭、迁移、凋亡的机制研究[J].安徽医药,2022,26(12):2354-2358. |
| 抗氧化反应元件信号通路调控胆囊癌细胞增殖、侵袭、迁移、凋亡的机制研究 |
| Mechanism of sanguinarine regulates gallbladder cancer cell proliferation, invasion, migration, and apoptosis via Kelch-like ECH-related protein 1/nuclear factor E2-related factor 2/antioxidant response element signaling pathway |
| |
| DOI：10.3969/j.issn.1009-6469.2022.12.005 |
| 中文关键词: 胆囊肿瘤 中草药 血根碱 Kelch样 ECH相关蛋白 1 核因子 E2相关因子 2 抗氧化反应元件 增殖 侵袭 迁移 凋亡 |
| 英文关键词: Gallbladder neoplasms Drugs, Chinese herbal Sanguinarine Kelch-like ECH-associated protein 1 Nuclear fac. tor E2-related factor 2 Antioxidant response element Proliferation Invasion Migration Apoptosis |
| 基金项目: |
|
| 摘要点击次数: 836 |
| 全文下载次数: 336 |
| 中文摘要: |
| 目的探讨血根碱调控胆囊癌细胞增殖、侵袭、迁移、凋亡的分子机制。方法于 2018年 1月至 2019年 9月体外培养人胆囊癌细胞 GBC-SD，用不同浓度( 2、4、8 μmol/L)的血根碱处理 48 h。MTT法检测细胞增殖抑制率； Transwell实验检测细胞迁移、侵袭能力；流式细胞术检测细胞凋亡率；采用荧光探针 DCFH-DA检测细胞内活性氧水平，应用多功能酶标仪检测丙二醛、还原型谷胱甘肽( GSH)含量与超氧化物歧化酶( SOD)活性；蛋白质印迹法检测增殖细胞核抗原( PCNA)、增殖标记蛋白细胞增殖核抗原 -67(Ki-67)、基质金属蛋白酶 -2(MMP-2)、基质金属蛋白酶 -9(MMP-9)、活化胱天蛋白酶 -3(cleaved-caspase-3)与 Kelch样 ECH相关蛋白 1(Keap1)/核因子 E2相关因子 2(Nrf2)/抗氧化反应元件( ARE)信号通路相关蛋白 Keap1、Nrf2、血红素加氧酶 1(HO-1)的表达量。结果与空白组相比，血根碱不同浓度组细胞增殖抑制率［( 2.07±0.68)%比( 12.49±1.53)%、(23.08±2.64)%、(44.67±3.68)%］显著升高( P<0.05)，迁移细胞数［( 243.19±15.48)个比( 146.34±12.56)个、(98.85±9.82)个、(75.79±7.37)个］与侵袭细胞数［( 136.68±8.37)个比( 97.43±7.15)个、(46.65±5.34)个、(38.15±4.53)个］显著减少( P<0.05)，PC. NA、Ki-67、MMP-2、MMP-9表达量显著降低( P<0.05)，细胞凋亡率［( 3.62±0.63)%比( 8.59±1.02)%、(14.16±1.14)%、(18.84±1.65)%］显著升高( P<0.05)，cleaved-caspase-3表达量显著升高( P<0.05)；与空白组相比，血根碱低浓度组、血根碱中浓度组、血根碱高浓度组活性氧、丙二醛水平显著升高( P<0.05)SOD活性与 GSH含量显著降低( P<0.05)Keap1、Nrf2、HO-1表达量显著降低(P<0.05)。结论/ARE信号通路从而抑制胆囊癌细胞侵袭、迁移，促进细胞凋亡。血根碱可能通过调控Keap1/Nrf2，增殖、， |
| 英文摘要: |
| Objective To investigate the molecular mechanism of sanguinarine regulating the proliferation, invasion, migration andapoptosis of gallbladder carcinoma cells.Methods Human gallbladder carcinoma cells GBC-SD were cultured in vitro from January2018 to September 2019, and treated with sanguinarine of different concentrations (2, 4, 8 μmol / L) for 48 h. MTT was used to detect cellproliferation inhibition rate. Transwell assay was used to detect cell migration and invasion. Flow cytometry was used to detect the apopto.sis rate. The fluorescence probe DCFH-DA was used to detect the intracellular ROS level, and the multifunctional microplate reader wasused to detect the content of MDA, GSH and the activity of SOD. Western blot was used to detect the expression of PCNA, Ki-67, MMP-2, MMP-9, cleaved-caspase-3 and Keap1 / Nrf2 / ARE signaling pathway related proteins Keap1, Nrf2, HO-1.Results Compared with the blank group, the inhibition rate [(2.07±0.68)% vs. (12.49±1.53)%, (23.08±2.64)%, (44.67±3.68)%] of cell proliferation was significantly increased in different groups of sanguinarine (P<0.05), and the number of migrating cells (243.19±15.48 vs. 146.34±12.56, 98.85±9.82, 75.79±7.37) and invasive cells (136.68±8.37 vs. 97.43±7.15, 46.65±5.34, 38.15±4.53) was significantly reduced (P<0.05), the expres. sion of PCNA, Ki-67, MMP-2, and MMP-9 was significantly reduced (P<0.05), the apoptosis rate [(3.62±0.63)% vs. (8.59±1.02)% , (14.16±1.14)%, (18.84±1.65)%] was significantly increased (P<0.05), and the expression of cleaved-caspase-3 was significantly in. creased (P<0.05). Compared with the blank group, the levels of ROS and MDA in the low concentration group, medium concentrationgroup, and high concentration group were significantly increased (P<0.05), the activity of SOD and the content of GSHweresignificantlyre. duced(P<0.05),tehexpressionlevelsofKeap1,Nrf2,andHO-1weresignificantlyreduced(P<0.05).Conclusion Sanguinarinemayinhibittheproliferation,invasion,andmigrationofgallbladdercarcinomacellsandpromoteapoptosisbyregulatingtheKeap1/Nrf2/AREsignalpathway. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
