康艾注射液通过IL-6/STAT3通路抑制胃癌细胞增殖

Chun-lei ZHENG; Ke-zuo HOU; An-qi WANG; Wan-xia FANG; Shi-tong YU; Jin-e LIANG; Hai-yan QI; Xiu-juan QU; Yun-peng LIU; Xiao-fang CHE

doi:10.1007/s11655-020-3265-6

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康艾注射液通过IL-6/STAT3通路抑制胃癌细胞增殖

Original Article | Updated：2022-06-27

- 康艾注射液通过IL-6/STAT3通路抑制胃癌细胞增殖
- Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway
- Chinese Journal of Integrative Medicine 2022年28卷第6期页码：524-530
- Affiliations：
  
  1.Department of Medical Oncology, the First Hospital of China Medical University, Shenyang (110001), China
  2.Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University,Shenyang (110001), China
  3.Liaoning Province Clinical Research Center for Cancer, Shenyang (110001), China
- Author bio：
  
  Associate Prof. CHE Xiao-fang, E-mail:xfche@cmu.edu.cn
- Funds：
  
  National Science and Technology Major Project of the Ministry of Science and Technology of China(2017ZX09304025);Construction Program of Clinical Cooperation Ability of Chinese and Western Medicine for Major and Difficult Diseases(2019-163);the Key Research and Development Program of Liaoning Province(2018225060);Science and Technology Plan Project of Liaoning Province(2016007010);Science and Technology Plan Project of Shenyang City(19-112-4-099)
- DOI：10.1007/s11655-020-3265-6
  中图分类号：
- 纸质出版日期：2022-06-01，
  
  网络出版日期：2020-07-09，
  
  录用日期：2019-12-26
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Chun-lei ZHENG, Ke-zuo HOU, An-qi WANG, 等. 康艾注射液通过IL-6/STAT3通路抑制胃癌细胞增殖[J]. Chinese Journal of Integrative Medicine, 2022,28(6):524-530.

Chun-lei ZHENG, Ke-zuo HOU, An-qi WANG, et al. Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway[J]. Chinese Journal of Integrative Medicine, 2022,28(6):524-530.
Chun-lei ZHENG, Ke-zuo HOU, An-qi WANG, 等. 康艾注射液通过IL-6/STAT3通路抑制胃癌细胞增殖[J]. Chinese Journal of Integrative Medicine, 2022,28(6):524-530. DOI： 10.1007/s11655-020-3265-6.

Chun-lei ZHENG, Ke-zuo HOU, An-qi WANG, et al. Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway[J]. Chinese Journal of Integrative Medicine, 2022,28(6):524-530. DOI： 10.1007/s11655-020-3265-6.

摘要

目的:

探讨中药康艾注射液 (KAI) 抑制胃癌细胞增殖的机制.

方法:

利用KAI (0、0.3%、1%、3%和10%)分别处理MGC803和BGC823胃癌细胞株24、48和72小时. MTT法检测细胞增殖活性; 流式细胞仪检测细胞凋亡和细胞周期; 采用实时定量聚合酶链反应(qRT-PCR)和酶联免疫吸附试验(ELISA)分别检测白细胞介素(IL)-6 mRNA及蛋白表达水平; Western blot检测细胞周期相关蛋白cyclinA/E/B1/D1、p21、RB及AKT、ERK、STAT1、STAT3的蛋白表达水平.

结果:

KAI以剂量和时间依赖方式抑制胃癌MGC803和BGC823细胞增殖. KAI处理胃癌细胞48小时后

G1期细胞比例增加

cyclinD1和磷酸化RB(p-RB) 表达水平降低

p21表达水平升高 (均

0.01) ; p-STAT3水平降低、IL-6 mRNA及蛋白表达水平受到抑制 (均

0.01) . 10 ng/mL IL-6可明显减弱3%和10% KAI对胃癌细胞增殖的抑制作用

部分恢复KAI抑制的STAT3磷酸化和细胞周期蛋白D1表达 (均

0.01) .

结论:

KAI通过抑制IL-6/STAT3信号通路诱导G1期阻滞而抑制胃癌细胞增殖.

Abstract

Objective:

To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.

Methods:

Gastric cancer cell lines MGC803 and BGC823 were treated by 0

0.3%

3% and 10% KAI for 24

48 and 72 h

respectively. The cell proliferation was evaluated by 3-(4

5-dimethyl-2-thiazolyl)-2

5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA)

respectively. The protein expression levels of cyclin A

cyclin E

cyclin B1

cyclin D1

p21

retinoblastoma (RB)

protein kinase B (AKT)

extracellular regulated protein kinases (ERK)

signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.

Results:

KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h

the proportion of G1 phase was increased

expression level of cyclin D1 and phosphorylation-RB were down-regulated

whereas the expression of p21 was up-regulated (all

0.01). Furthermore

48-h treatment with KAI decreased the phosphorylation level of STAT3

inhibited the mRNA and protein expressions of IL-6 (all

0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI

and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all

0.01).

Conclusion:

KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G

phase arrest in gastric cancer cells.

关键词

Keywords

Kang-Ai Injectiongastric cancerG1 arrestinterleukin-6signal transducer and activator of transcription 3Chinese herbal medicine

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