24-羟基-人参二醇的抗癌作用及基于分子对接的机制

郑茜; 王朝晖; 祁增; 李平亚

doi:10.13422/j.cnki.syfjx.20190622

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24-羟基-人参二醇的抗癌作用及基于分子对接的机制

药理 | 更新时间：2021-02-09

- 24-羟基-人参二醇的抗癌作用及基于分子对接的机制
- Anticancer Effect and Molecular Docking Mechanism of 24-OH-panaxadiol
- 中国实验方剂学杂志 2019年25卷第6期页码：81-88
- 作者机构：
  
  1.山西医科大学，太原　 030001；
  2.吉林大学　药学院，长春　 130021；
  3.哈佛大学　医学院　麻省总医院　移植研究中心，波士顿　 02129
- 作者简介：
  
  郑茜，博士，在站博士后，讲师，从事药物化学结构及其生物活性研究，E-mail：qianz88@163.com
  李平亚，博士，教授，从事天然药物化学成分及其生物活性研究，E-mail：lipy@jlu.edu.cn
- 基金信息：
  
  吉林省科技成果转化计划项目(201603033YY);吉林省重大科技项目(吉人才办[2016]3号);中国博士后科学基金项目(2018M641678)
- DOI：10.13422/j.cnki.syfjx.20190622
  中图分类号： R22;R242;R2-031;R285.5
- 收稿日期：2018-07-10，
  
  网络出版日期：2018-12-12，
  
  纸质出版日期：2019-03-20
- 稿件说明：
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郑茜, 王朝晖, 祁增, 等. 24-羟基-人参二醇的抗癌作用及基于分子对接的机制[J]. 中国实验方剂学杂志, 2019,25(6):81-88.

Qian ZHENG, Zhao-hui WANG, Zeng QI, et al. Anticancer Effect and Molecular Docking Mechanism of 24-OH-panaxadiol[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 81-88.
郑茜, 王朝晖, 祁增, 等. 24-羟基-人参二醇的抗癌作用及基于分子对接的机制[J]. 中国实验方剂学杂志, 2019,25(6):81-88. DOI： 10.13422/j.cnki.syfjx.20190622.

Qian ZHENG, Zhao-hui WANG, Zeng QI, et al. Anticancer Effect and Molecular Docking Mechanism of 24-OH-panaxadiol[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(6): 81-88. DOI： 10.13422/j.cnki.syfjx.20190622.

摘要

目的：

为研究人参皂苷20(

)-达玛-20，25-环氧-3

，12

，24

-三醇(24-OH-PD)对多种癌细胞的增殖抑制及诱导凋亡作用并探讨其作用机制。

方法：

采用噻唑蓝(MTT)比色法或CellTiter Glo®发光试验检测24-OH-PD在不同质量浓度(12.5，25，50，100 mg·L

－1

)，不同作用时间(24，48，72 h)下对CCRF-CEM

Jeko-1

M14

MD-MBA-231癌细胞的增殖抑制作用，并与20(

)-Rg

，20(

)-Rh

进行比较。采用流式细胞术检测24-OH-PD对以上4种癌细胞的凋亡诱导作用。采用药物设计平台薛定谔Maestro 6.7软件对癌症相关的40种蛋白与24-OH-PD进行分子对接研究。

结果：

24-OH-PD对4种癌细胞均具有明显的细胞活性抑制作用，且具有时间、剂量依赖性。24-OH-PD对CCRF-CEM，Jeko-1，M14，MD-MBA-231细胞作用48 h时半抑制浓度(IC

)分别为25.36，39.29，21.74，19.35 mg·L

－1

，与20(

)-Rh

作用效果相似(IC

分别为23.35

65.79

18.95

19.67 mg·L

－1

)；远远强于20(

)-Rg

，仅对Jeko-1细胞有抑制作用(IC

49.5 mg·L

－1

)。磷脂结合蛋白V/碘化吡啶(Annexin V/PI)双染实验结果显示，24-OH-PD对4种细胞均具有不同程度的促凋亡作用(

0.05)，且具有剂量依赖关系。分子对接实验表明32个癌症相关蛋白中有11个能够与24-OH-PD对接成功，包括嘌呤核苷磷酸化酶(PNP)，蛋白络氨酸激酶，蛋白激酶C(PKC)，B淋巴细胞瘤基因-2(Bcl-2)，B淋巴细胞瘤基因-xl (Bcl-xl)，含半胱氨酸的天冬氨酸蛋白水解酶-8等，表明24-OH-PD的抗肿瘤作用可能与直接作用于这些蛋白相关。

结论：

人参皂苷24-OH-PD对CCRF-CEM，M14，MD-MBA-231，Jeko-1癌细胞具有增殖抑制作用，其机制可能与PNP，PKC等蛋白相关；同时24-OH-PD还具有诱导癌细胞凋亡的作用，机制可能与Bcl-2，Bcl-xl等蛋白相关。

Abstract

Objective:

To investigate the effect of ginsenoside 20(

)

25-epoxydammarane-3

-triol (24-OH-panaxadiol

24-OH-PD) on inhibiting proliferation and inducing apoptosis of tumor cells

and explore its mechanism of action.

Method:

The inhibitory effect of 24-OH-PD (12.5

100 mg·L

-1

) on proliferation of CCRF-CEM

M14

MD-MBA-231 and Jeko-1 cells with different treatment periods (24

72 h) was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT)assay and CellTiter Glo® test

and the results were then compared with 20(

)-Rg

and 20(

)-Rh

.Flow cytometry was used to detect cell apoptosis caused by 24-OH-PD. Besides

the potential anticancer mechanism was studied by docking analysis with 40 cancer related proteins and 24-OH-PD by using drug design platform Schrodinger Maestro 6.7 Software.

Result:

24-OH-PD inhibited the proliferation of all the 4 cancer cell lines significantly in a time and dosage dependent manner. The IC

value of 24-OH-PD on CCRF-CEM

Jeko-1

M14

and MD-MBA-231 cell lines was 25.36

39.29

21.74

and 19.35 mg·L-1

respectively

similar to 20(

)-Rh

(IC

23.35

65.79

18.95

19.67 mg·L

-1

) and much better than 20(

)-Rg

(only effective for Jeko-1 cells

49.5 mg·L

-1

). Annexin V/PI double staining experiment showed that 24-OH-PD could also induce apoptosis of the 4 kinds of cancer cells (

0.05) in a dose-dependent manner. In the molecular docking test

24-OH-PD was docked successfully with 11 tumor related proteins

including purine nucleoside phosphorylase (PNP)

protein tyrosine kinase

protein kinase C (PKC)

B-cell lymphoma-2 (Bcl-2)

B-cell lymphoma-xl (Bcl-xl) and Caspase-8 et al

which demonstrated that the anti-tumor effect of 24-OH-PD may be related to the direct effects on these proteins.

Conclusion:

24-OH-PD could inhibit cell proliferation and induce apoptosis for CCRF-CEM

M14

MD-MBA-231 and Jeko-1 cell lines

which may through directly acting on Bcl-2

Bcl-xl

and other proteins.

关键词

Keywords

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