四君子汤通过降低β-catenin转录活性抑制胃癌肿瘤干细胞干性

Yue-jun LI; Lin-li LIAO; Pei LIU; Ping TANG; Hong WANG; Qing-hua PENG

doi:10.1007/s11655-021-3314-9

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四君子汤通过降低β-catenin转录活性抑制胃癌肿瘤干细胞干性

Original Article | Updated：2022-07-20

- 四君子汤通过降低β-catenin转录活性抑制胃癌肿瘤干细胞干性
- Sijunzi Decoction Inhibits Stemness by Suppressing β-Catenin Transcriptional Activity in Gastric Cancer Cells
- Chinese Journal of Integrative Medicine 2022年28卷第8期页码：702-710
- Affiliations：
  
  1.Department of Oncology, the Third Affiliated Hospital of Hunan University of Chinese Medicine, Zhuzhou (412000),Hunan Province, China
  2.Department of Oncology, the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine, Zhuzhou (412000), Hunan Province, China
  3.Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine,Changsha (410208), China
- Author bio：
  
  Prof. PENG Qing-hua, E-mail: pqh410007@126.com
- Funds：
  
  National Natural Science Foundation of China(81703916);Natural Science Foundation of Hunan Province(2018JJ6042)
- DOI：10.1007/s11655-021-3314-9
  中图分类号：
- 纸质出版日期：2022-08，
  
  网络出版日期：2021-11-09，
  
  录用日期：2021-05-17
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Yue-jun LI, Lin-li LIAO, Pei LIU, 等. 四君子汤通过降低β-catenin转录活性抑制胃癌肿瘤干细胞干性[J]. Chinese Journal of Integrative Medicine, 2022,28(8):702-710.

Yue-jun LI, Lin-li LIAO, Pei LIU, et al. Sijunzi Decoction Inhibits Stemness by Suppressing β-Catenin Transcriptional Activity in Gastric Cancer Cells[J]. Chinese Journal of Integrative Medicine, 2022,28(8):702-710.
Yue-jun LI, Lin-li LIAO, Pei LIU, 等. 四君子汤通过降低β-catenin转录活性抑制胃癌肿瘤干细胞干性[J]. Chinese Journal of Integrative Medicine, 2022,28(8):702-710. DOI： 10.1007/s11655-021-3314-9.

Yue-jun LI, Lin-li LIAO, Pei LIU, et al. Sijunzi Decoction Inhibits Stemness by Suppressing β-Catenin Transcriptional Activity in Gastric Cancer Cells[J]. Chinese Journal of Integrative Medicine, 2022,28(8):702-710. DOI： 10.1007/s11655-021-3314-9.

摘要

目的:

探讨四君子汤对胃癌细胞的抑制作用及分子机制.

方法:

MKN74和MKN45是两种具有干细胞性质的CD44阳性胃癌细胞系. 将细胞分为治疗组及对照组. 治疗组给予四君子汤水提醇沉物(1-5 mg/mL)治疗

疗程48 h-14 d. 对照组给予等体积的磷酸盐缓冲盐水治疗. 采用细胞计数试剂盒8 (CCK-8) 法测定细胞活力. 通过克隆成球实验和胃癌肿瘤干细胞标记物表达检测胃癌肿瘤干细胞干性. 采用核质分离实验和染色质免疫共沉淀法分别测定四君子汤水提醇沉物处理后β-catenin的细胞内分布和DNA结合活性.

结果:

四君子汤水提醇沉物抑制MKN74和MKN45细胞株的生长并诱导其凋亡(

0.05). 四君子汤水提醇沉物可明显抑制胃癌细胞克隆成球能力和胃癌肿瘤干细胞标记物的表达(

0.05). 在分子机制上

β-catenin是维持胃癌肿瘤干细胞干性的关键调控因子. 四君子汤水提醇沉物科明显降低β-catenin的细胞核内聚集和DNA结合活性(

0.05).

结论:

四君子汤通过降低β-catenin转录活性

抑制胃癌肿瘤干细胞干性.

Abstract

Objective:

To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs).

Methods:

MKN74 and MKN45

two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1–5 mg/mL) for indicated time (48 h–14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs stemness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of β-catenin after SJZD treatment

respectively.

Results:

SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (

0.05). Moreover

SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (

0.05). Mechanistically

SJZD reduced nuclear accumulation and DNA binding activity of β-catenin (

0.05)

the key regulator for maintaining CSC stemness.

Conclusion:

SJZD inhibits GCSCs by attenuating the transcriptional activity of β-catenin.

关键词

Keywords

Sijunzi DecoctionChinese medicinegastric cancercancer stem cellsβ-catenin

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