吴茱萸碱通过MAPK信号通路抑制人胃癌细胞的体外实验研究

千维娜; 李治; 方瑜; 姜伊娜; 肖海娟

doi:10.16016/j.1000-5404.202103002

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吴茱萸碱通过MAPK信号通路抑制人胃癌细胞的体外实验研究

基础医学 | 更新时间：2026-01-09

- 吴茱萸碱通过MAPK信号通路抑制人胃癌细胞的体外实验研究
- Anti-tumor mechanism of evodiamine on gastric cancer cells in vitro through MAPK signaling pathway
- 第三军医大学学报 2021年43卷第16期页码：1535-1542
- 作者机构：
  
  1.712000 陕西咸阳，陕西中医药大学: 附属医院肿瘤科
  2.712000 陕西咸阳，陕西中医药大学: 药学院
  3.712000 陕西咸阳，陕西中医药大学: 基础医学院
- 作者简介：
  
  [肖海娟，E-mail: daisytcm@hotmail.comXIAO Haijuan, E-mail: daisytcm@hotmail.com
- 基金信息：
  
  国家自然科学基金面上项目(82074255);陕西省自然科学基础研究计划项目(2020JQ-859)
- DOI：10.16016/j.1000-5404.202103002
  中图分类号： R282.71;R285.5;R735.2
- 收稿：2021-03-01，
  
  修回：2021-04-27，
  
  纸质出版：2021-08-30
- 稿件说明：
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千维娜, 李治, 方瑜, 等. 吴茱萸碱通过MAPK信号通路抑制人胃癌细胞的体外实验研究[J]. 第三军医大学学报, 2021,43(16):1535-1542.

Weina QIAN, Zhi LI, Yu FANG, et al. Anti-tumor mechanism of evodiamine on gastric cancer cells in vitro through MAPK signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(16): 1535-1542.
千维娜, 李治, 方瑜, 等. 吴茱萸碱通过MAPK信号通路抑制人胃癌细胞的体外实验研究[J]. 第三军医大学学报, 2021,43(16):1535-1542. DOI： 10.16016/j.1000-5404.202103002.

Weina QIAN, Zhi LI, Yu FANG, et al. Anti-tumor mechanism of evodiamine on gastric cancer cells in vitro through MAPK signaling pathway[J]. Journal of Third Military Medical University, 2021, 43(16): 1535-1542. DOI： 10.16016/j.1000-5404.202103002.

摘要

目的

探讨吴茱萸碱通过丝裂原活化蛋白激酶(mitogen-activated protein kinase

MAPK)信号通路对人胃癌细胞的抑制作用。

方法

应用MTT法对SGC-7901细胞活性进行评定。以8、16、32 μmol/L吴茱萸碱作用胃癌SGC-7901细胞(记为A

组，A

组)，另设置相同浓度吴茱萸碱处理后的细胞，加入p38抑制剂(记为B

组，B

组)，对照组用细胞培养液处理作为空白对照。Annexin V-FITC/PI法观察细胞凋亡，PI染色法观察细胞周期，Western blot检测凋亡相关蛋白Bcl-2、cleaved-caspase-3，划痕愈合实验评价细胞迁移抑制情况，蛋白质印迹法检测c-dc2、cdc25C、cyclin B1及p-ERK、p-p38蛋白水平表达。

结果

吴茱萸碱能够阻碍SGC-7901细胞增殖，细胞活性随着浓度和时间的增加而降低，24、48 h的IC

分别是16.78、7.28 μmol/L。

与对照组(0.06%)比较，A组SGC-7901细胞凋亡比例(18.72%、31.08%、52.17%)增加，G

/M细胞周期阻滞，与A组比较，B组SGC-7901细胞凋亡比例减少，G

/M细胞周期阻滞减弱，G

/M期调控蛋白cdc2、cdc25C、cyclin B1水平下调(

均＜0.05)。划痕愈合实验表明SGC-7901细胞的细胞划痕愈合率伴随吴茱萸碱浓度升高而降低；与A组(59.13%、23.15%、18.31%)比较，B组细胞划痕愈合率(63.17%、55.27%、34.08%)升高(

＜0.05)。Western blot结果表明吴茱萸碱处理Bcl-2、cleaved-caspase-3水平上调，SGC-7901细胞MAPK通路蛋白p-ERK水平下调，p-p38表达水平上调(

＜0.05)。与A组比较，B组cdc2、cdc25C、cyclin B1表达上调，Bcl-2、cleaved-caspase-3水平显著下降，MAPK通路蛋白p-ERK水平上调，p-p38水平下调(

＜0.05)。

结论

吴茱萸碱对胃癌细胞有抑制作用，其机制是通过MAPK信号通路下调p-p38蛋白、上调凋亡蛋白实现。

Abstract

Objective

To investigate the anti-tumor effect of evodiamine on gastric cancer cells

via

the MAPK signaling pathway.

Methods

MTT assay was used to assess the cell viability of SGC-7901 cells after the treatment of 8

16 and 32 μmol/L evocarpine (denoted as A

group

group). The effect of p38 inhibitor on the above cells (denoted as B

group

group) were studied. The blank control cell group was the cells treated with culture medium. Annexin V-FITC/PI was used to observe cell apoptosis

PI staining to observe cell cycle

Western blotting to measure apoptosis-related proteins Bcl-2 and cleaved-caspase-3

and scratch healing test to evaluate the inhibitory effect on cell migration. Western blotting was employed to detect the expression levels of c-dc2

cdc25C

cyclin B1

and p-ERK and p-p38.

Results

Evodiamine negatively inhibited the proliferation of SGC-7901 cells in a dose-dependent and time-dependent manner. The IC

values at 24 and 48 h were 16.78 and 7.28 μmol/L

respectively. Compared with the control group (0.06%)

the apoptotic rate of SGC-7901 cells was increased in groups A

and A

(18.72%

31.08% and 52.17%)

and the cells arrested at G

/M phase. The proportion of apoptotic cells in group B was decreased

there were less cells arrested at G

/M phase

and the expression of G

/M phase regulatory proteins CDC2

CDC25C and Cyclin B1 were down-regulated when compared with group A (all

0.05). The scratch healing test showed that the healing rate of SGC-7901 cells was decreased with the increase of evodiamine concentration. Compared with groups A

and A

(59.13%

23.15% and 18.31%)

the rate was increased in groups B

and B

(63.17%

55.27%

34.08%

0.05). Western blot results indicated that evodiamine treatment induced the up-regulation of Bcl-2 and cleaved caspase-3

down-regulation of p-ERK

and obvious elevation of p-p38 (

0.05). Compared with group A

the expression levels of CDC2

CDC25C and Cyclin B1 were increased

those of Bcl-2 and cleaved caspase-3 were significantly decreased

while that of p-ERK was up-regulated and that of p-p38 was down-regulated in group B (

0.05).

Conclusion

Evodiamine shows anti-tumor effect on gastric cancer cells

and it is realized by the down-regulation of p-p38 protein and up-regulation of apoptosis-related proteins through MAPK signaling pathway.

关键词

Keywords

references

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