黄芩素对人肺腺癌A549细胞的药效作用及机制探讨

曹慧娟; 李君; 孙淑军; 房军伟; 王洋; 张永煜; 毛文伟

doi:10.13422/j.cnki.syfjx.2017020098

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黄芩素对人肺腺癌A549细胞的药效作用及机制探讨

药理 | 更新时间：2024-01-04

- 黄芩素对人肺腺癌A549细胞的药效作用及机制探讨
- Pharmacodynamic Effect and Mechanism of Baicalein on Lung Adenocarcinoma A549 Cells
- 中国实验方剂学杂志 2017年23卷第2期页码：98-103
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目（81373519）;上海市科技创新行动计划项目（13401900306）;华北理工大学博士科研课题启动基金项目（25758399）
- DOI：10.13422/j.cnki.syfjx.2017020098
  中图分类号： R285
- 纸质出版日期：2017
- 稿件说明：
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曹慧娟, 李君, 孙淑军, 等. 黄芩素对人肺腺癌A549细胞的药效作用及机制探讨[J]. 中国实验方剂学杂志, 2017,23(2):98-103.

CAO Hui-juan, LI-jun, SUN Shu-jun, et al. Pharmacodynamic Effect and Mechanism of Baicalein on Lung Adenocarcinoma A549 Cells[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(2): 98-103.
曹慧娟, 李君, 孙淑军, 等. 黄芩素对人肺腺癌A549细胞的药效作用及机制探讨[J]. 中国实验方剂学杂志, 2017,23(2):98-103. DOI： 10.13422/j.cnki.syfjx.2017020098.

CAO Hui-juan, LI-jun, SUN Shu-jun, et al. Pharmacodynamic Effect and Mechanism of Baicalein on Lung Adenocarcinoma A549 Cells[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(2): 98-103. DOI： 10.13422/j.cnki.syfjx.2017020098.

摘要

目的：研究黄芩素对A549细胞增殖、侵袭、迁移，对人脐静脉血管内皮细胞（HUVEC）血管形成的影响；观察其体内对裸鼠移植瘤的作用，通过代谢组学探讨其抑瘤机制。方法：体外实验，噻唑蓝（MTT）法检测黄芩素对A549细胞生长的影响；transwell小室法观察黄芩素对A549细胞侵袭及迁移的影响；小管生成实验观察黄芩素对HUVEC新生血管形成的影响。体内实验，移植瘤裸鼠分为模型组、顺铂组、黄芩素（50，100 μmol·L-1）组，观察黄芩素对移植瘤的干预作用；气相色谱/质谱法对黄芩素干预后裸鼠血清样本进行代谢组学分析，寻找差异性代谢物及代谢通路。结果：黄芩素能抑制A549细胞生长，24，48，72 h的IC50分别为43.02，31.11，28.42 μmol·L-1。黄芩素（5，10，20 μmol·L-1）能抑制A549细胞的侵袭及迁移。黄芩素（10，20 μmol·L-1）能抑制HUVEC官腔样结构的形成（P<0.05）。黄芩素（50 mg·kg-1）对移植瘤具有抑制作用；代谢组学方法检测到黄芩素组血清中差异性代谢物14种，代谢通路7条。结论：黄芩素可抑制A549细胞增殖、侵袭、迁移及HUVEC官腔样结构形成，体内对移植瘤生长具有抑制作用；黄芩素干预后，血清中氨基酸、碳水化合物、能量代谢等多条代谢通路发生变化，这些变化可能是其抗肿瘤的作用机制。

Abstract

Objective: To study the effects of baicalein on the proliferation

invasion and migration of A549 cells

and investigate its effects on vascularization of human umbilical vein endothelial cells (HUVEC)

as well as the antitumor effect of baicalein on A549 cell xenografts in vivo

and the antitumor mechanism of baicalein by the method of serum metabnomics. Method: In vitro

the thiazolyl blue terazolium bromide (MTT) assay was used to detect the effect of baicalein on A549 cells proliferation. The effect of baicalein on invasion and migration of A549 cells were detected by transwell assay. The anti-angiogenic effect of baicalein on HUVEC was detected by tubule formation experiment. In vivo:anti-tumor efficacy of baicalein was evaluated in nude mice models of human lung cancer xenograft. The nude mice were divided into model group

cisplatin group

and baicalein groups (50

100 μmol·L-1). The serum samples from nude mice were subjected to metabolomics analysis after baicalein treatment by using gas chromatography/mass spectrometry (GC/MS)

looking for the differential metabolites and related metabolic pathways. Result: The growth of A549 cells was significantly inhibited by different concentrations of baicalein

and the 50% concentration of inhibition(IC50) of baicalein were 43.02

31.11

28.42 μmol·L-1 respectively at 24 h

48 h and 72 h. Different concentrations of baicalein (5

20 μmol·L-1) could inhibit the invasion and migration abilities of A549 cells. Baicalein (10

20 μmol·L-1) could inhibit the tubule structure formation of HUVEC (P<0.05). The growth of A549 cell xenograft was inhibited by baicalein (50 mg·kg-1) in vivo. A total of 14 differential metabolites and 7 related metabolic pathways in the serum were found after intervention with baicalein. Conclusion: Baicalein could inhibit the proliferation

invasion and migration of A549 cells and the tubule formation of HUVEC in vitro

with inhibitory effect on the growth of A549 cell xenograft. The changed metabolic pathways in the baicalein group including amino acid metabolism

carbohydrate metabolism and energy metabolism in the serum were found

and the antitumor mechanism of baicalein maybe relevant to these metabolic pathways.

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