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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (6): 601-608.doi: 10.12092/j.issn.1009-2501.2023.06.001

• 基础研究 •    下一篇

AMI-1通过下调PRMT5表达对胰腺癌细胞体外活性的影响

张景惠1,2,卫浩亮1,2,王  丽1,2,李京凯1,2,张宝来3,杨孝来1,2,3   

  1. 1甘肃中医药大学药学院药理教研室,兰州  730000,甘肃;
    2甘肃省人民医院药剂科,兰州  730000,甘肃;
    3兰州大学药理研究所,兰州  730000,甘肃

  • 收稿日期:2022-12-21 修回日期:2023-05-20 出版日期:2023-06-26 发布日期:2023-07-12
  • 通讯作者: 杨孝来,男,教授,硕士生导师,研究方向:肿瘤药理学。 E-mail:yxl1668@vip.163.com
  • 作者简介:张景惠,女,硕士在读,研究方向:肿瘤药理学。 E-mail:z248274@163.com
  • 基金资助:
    国家自然科学基金地区项目(81560595)

Effects of AMI-1 on the activity of pancreatic cancer cells in vitro by down-regulating PRMT5 expression

ZHANG Jinghui1,2, WEI Haoliang1,2, WANG Li1,2, LI Jingkai1,2, ZHANG Baolai3, YANG Xiaolai1,2,3   

  1. 1College of pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China; 2Department of Pharmacy, People’s Hospital of Gansu Province, Lanzhou 730000, China; 3Department of Pharmacology, School of Medicine, Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2022-12-21 Revised:2023-05-20 Online:2023-06-26 Published:2023-07-12

摘要:

目的:研究AMI-1对人胰腺癌MIAPaca-2细胞增殖、迁移、凋亡的影响及其机制。方法:以MIAPaca-2细胞为研究对象,分别设立对照组,不同浓度AMI-1(0.6、1.2、2.4 mmol/L)处理组。采用MTT、克隆形成实验、Transwell和划痕实验分别检测AMI-1对MIAPaca-2细胞增殖、克隆、迁移的影响;流式细胞术检测细胞凋亡;Western blot检测AMI-1对MIAPaca-2细胞中caspase3、cleaved-caspase3、PRMT5、H4R3me2s、PCNA蛋白表达的影响。结果:与对照组相比,不同浓度AMI-1处理后,MIAPaca-2细胞的存活率逐渐降低,呈浓度和时间依赖性(P<0.01);细胞克隆形成率减少(P<0.01),细胞迁移能力减弱(P<0.01),细胞凋亡率升高(P<0.01),cleaved-caspase3/caspase3蛋白表达升高(P<0.01),PRMT5、H4R3me2s和PCNA的蛋白表达降低(P<0.01)。结论:AMI-1能够抑制胰腺癌细胞体外生长增殖、迁移和诱导凋亡,可能与AMI-1下调PRMT5、H4R3me2s和PCNA的表达,上调cleaved-caspase3/caspase3的表达有关。

关键词: AMI-1, 胰腺癌, PRMT5, 体外活性

Abstract:

AIM: To explore the effect and mechanism of AMI-1 on the proliferation, migration and apoptosis of human pancreatic cancer MIAPaca-2 cells. METHODS: MIAPaca-2 cells were randomly divided into the control groups and the treatment groups with different concentrations of AMI-1 (0.6, 1.2 and 2.4 mmol/L). MTT assay, colony formation assay, scratch assay and Transwell assay respectively were used to detect the effects of AMI-1 on the proliferation, colony formation and migration of MIAPaca-2 cells. The cell apoptosis was detected by flow cytometry. The effect of AMI-1 on the protein expression of caspase3, cleaved-caspase3, PRMT5, H4R3me2s and PCNA in MIAPaca-2 cells were detected by western blot. RESULTS: Compared with control group, after treatment with different concentrations of AMI-1, the cell survival rate of MIAPaca-2 cells decreased gradually in a time- and dose-dependent manner (P<0.01), the rate of cell clone formation decreased (P<0.01), the cell migration ability were diminished (P<0.01), the apoptosis rate was increased (P<0.01), and the protein level of cleaved-caspase3/caspase3 were increased, the protein level of PRMT5, H4R3me2s and PCNA were reduced (P<0.01). CONCLUSION: AMI-1 significantly inhibited the proliferation migration and apoptosis of pancreatic cancer cells in vitro, which may be associated with AMI-1 down-regulating the expression of PRMT5, H4R3me2s and PCNA, and up-regulation the expression of cleaved-caspase3/caspase3.

Key words: AMI-1, pancreatic cancer, PRMT5, in vitro activity

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