中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (34): 5460-5466.doi: 10.3969/j.issn.2095-4344.2017.34.009

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

冬凌草甲素固体脂质纳米粒干预食管癌细胞的增殖

陈晓琦1,蒋  晶2,陈欣菊1,张传雷1,王新亭1,冀爱英1   

  1. 1河南中医药大学第一附属医院,河南省郑州市  450000;2郑州大学,微纳成型技术国家级国际联合研究中心,河南省郑州市  450000
  • 收稿日期:2017-08-03 出版日期:2017-12-08 发布日期:2018-01-04
  • 通讯作者: 陈欣菊,主任医师,河南中医药大学第一附属医院,河南省郑州市 450000
  • 作者简介:陈晓琦,1984年生,河南省商丘市人,汉族,2015年郑州大学毕业,博士,主治医师,主要从事消化道常见肿瘤的基础与临床研究。
  • 基金资助:

    河南省科技攻关计划项目(162102310106);2017年河南省高等学校基础研究项目(17B320005)

Oridonin solid lipid nanoparticles inhibit proliferation of esophageal cancer cells

Chen Xiao-qi1, Jiang Jing2, Chen Xin-ju1, Zhang Chuan-lei1, Wang Xin-ting1, Ji Ai-ying1
  

  1. 1The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China; 2the National & International Research Center for Micro-Nano Molding Technology, Zhengzhou University, Zhengzhou 450000, Henan Province, China
  • Received:2017-08-03 Online:2017-12-08 Published:2018-01-04
  • Contact: Chen Xin-ju, Chief physician, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • About author:Chen Xiao-qi, M.D., Attending physician, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • Supported by:
     the Scientific Tackle Key Project of Henan Province, No. 162102310106; the 2017 Basic Research Project of Higher Education in Henan Province, No. 17B320005

摘要:

文章快速阅读:

 

文题释义:
固体脂质体纳米粒:是一种用可生物降解载体材料制作的具有较好靶向性和缓控释作用的剂型,具有抗肿瘤活性,由紫杉醇、阿霉素等抗肿瘤药物制成的固体脂质体纳米粒能抑制乳腺癌等多种肿瘤细胞的增殖,且比单纯药物效果好。
Wnt/β-catenin信号通路:是Wnt信号通路中的经典通路,参与了包括细胞凋亡及坏死等多种生命活动过程。其通路包括核转录因子、Wnt蛋白、跨膜受体胞质蛋白及下游的靶基因等。当Wnt信号通路被激活时,可通过一系列过程激活下游的CyclinD1、c-myc等靶基因,影响细胞增殖、凋亡过程。在乳腺癌、黑色素瘤、胃癌等多种肿瘤细胞中存在Wnt信号通路的异常激活,可促进肿瘤细胞的发生发展。
 
背景:越来越多的研究显示由中药制成的固体脂质纳米粒有抑制癌细胞增殖、诱导细胞凋亡的作用。
目的:探讨冬凌草甲素固体脂质纳米粒对食管癌细胞增殖和凋亡的影响。
方法:①0,2.5,5,10,20 μmol/L冬凌草甲素固体脂质纳米粒作用于人食管癌Eca-109细胞24,48,72 h后,CCK8检测细胞抑制率,计算IC50;②0,14 μmol/L冬凌草甲素固体脂质纳米粒作用人食管癌Eca-109细胞48 h后,流式细胞仪检测细胞凋亡率;③Western blot检测Cleaved caspase3、β-catenin、C-myc、Cyclin D1蛋白表达;④Wnt/β-catenin信号通路激活剂氯化锂及氯化锂+冬凌草甲素固体脂质纳米粒作用于人食管癌Eca-109细胞48 h后,再检测上述相关指标,对照组细胞不做任何处理。
结果与结论:①不同浓度的冬凌草甲素固体脂质纳米粒作用于食管癌细胞24,48,72 h后的细胞抑制率均显著高于0 h时的细胞抑制率,且随着时间延长及浓度增加细胞抑制率增加(P < 0.01);②14 μmol/L组细胞凋亡率及Cleaved caspase3蛋白表达均显著高于0 μmol/L组,β-catenin、C-myc、Cyclin D1蛋白表达均显低于0 μmol/L组(P < 0.01);③激活剂组及激活剂+冬凌草甲素固体脂质纳米粒组细胞抑制率、凋亡率及Cleaved caspase3蛋白表达均显著高于对照组,β-catenin、C-myc、Cyclin D1蛋白表达均显著低于对照组(P < 0.01);④激活剂+冬凌草甲素固体脂质纳米粒组细胞抑制率、凋亡率及Cleaved caspase3蛋白表达显著低于激活剂组,β-catenin、C-myc、Cyclin D1蛋白表达显著高于激活剂组(P < 0.01);⑤结果表明,冬凌草甲素固体脂质纳米粒可抑制人食管癌Eca-109细胞增殖并促进细胞凋亡,其机制与Wnt/β-catenin信号通路的调控有关。

关键词: 生物材料, 纳米材料, 冬凌草甲素固体脂质纳米粒, Wnt/β-catenin信号通路, 食管癌, 增殖, 凋亡

Abstract:

BACKGROUND: Increasing studies have shown that solid lipid nanoparticles made from traditional Chinese medicine can inhibit cancer cell proliferation and induce cell apoptosis.
OBJECTIVE: To investigate the mechanisms of oridonin solid lipid nanoparticles (ORI-SLN) by the regulation of Wnt/β-catenin signaling pathway on the proliferation and apoptosis of esophageal cancer cells.
METHODS: After 0, 2.5, 5, 10, 20 μmol/L ORI-SLN treated human esophageal cancer cell lines Eca-109 for 24, 48, 72 hours, the cell inhibition rate was detected by cell counting kit-8, and the half maximal inhibitory concentration (IC50) was calculated. After 0, 14 μmol/L ORI-SLN treated Eca-109 cells for 48 hours, the cell apoptosis was detected by flow cytometry. The expression of Cleaved caspase3, β-catenin, C-myc, Cyclin D1 proteins was detected by western blot assay. Wnt/β-catenin signaling pathway activator LiCl and LiCl+ORI-SLN were used to treat Eca-109 cells for 48 hours, and then the relevant indicators were reexamined. Eca-109 cells without any treatment were used as controls.
RESULTS AND CONCLUSION: The cell inhibition rate of Eca-109 cells treated with different concentrations of ORI-SLN for 24, 48 and 72 hours was significantly higher than that at 0 hour, and the cell inhibition rate was found to increase with the prolongation of time and the increase of the concentration (P < 0.01). 14 μmol/L ORI-SLN was confirmed to result in the higher cell apoptosis and Cleaved caspase3 expression compared with the 0 μmol/L group, while the expression of β-catenin, C-myc, Cyclin D1 proteins were significantly lower than the 0 μmol/L group (P < 0.01). Cell inhibition rate, apoptosis rate and Cleaved caspase3 protein expression in the activator group and ORI-SLN+activator group were significantly higher than those in the control group, and the expression of β-catenin, C-myc, Cyclin D1 protein was significantly lower than those in the control group (P < 0.01). The cell inhibition rate, apoptosis rate and expression of Cleaved caspase3 in ORI-SLN+activator group was significantly lower than those in the activator group, and the β-catenin, C-myc, Cyclin D1 protein expression was significantly higher than that in the activator group (P < 0.01). To conclude, ORI-SLNs can inhibit the proliferation and apoptosis of human esophageal carcinoma cell line Eca-109, and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway. 

Key words: Nanoparticles, Liposomes, Rabdosia, Esophageal Neoplasms, Cell Proliferation, Apoptosis, Tissue Engineering

中图分类号: