Mechanism of Weichang'an in inhibiting malignant progression of gastric cancer cells through alternative splicing of inhibitor of differentiation 1

ZHU Jiangchuan; CAO Nida; MA Fangqi; CHEN Bin; SUN Xiaoyu; DONG Jiahuan; ZHANG Guangtao; WANG Yi; SHEN Yumiao; ZHAO Aiguang

doi:10.16305/j.1007-1334.2025.z20250312003

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Mechanism of Weichang'an in inhibiting malignant progression of gastric cancer cells through alternative splicing of inhibitor of differentiation 1

更新时间：2025-12-12

- Mechanism of Weichang'an in inhibiting malignant progression of gastric cancer cells through alternative splicing of inhibitor of differentiation 1
- Shanghai Journal of Traditional Chinese Medicine Vol. 59, Issue 12, Pages: 70-75(2025)
- 作者机构：
  
  1.上海中医药大学附属龙华医院肿瘤一科（上海 200032）
  2.中国科学技术大学附属第一医院中医科（安徽合肥 230001）
  3.上海中医药大学附属普陀医院中医肿瘤科（上海 200062）
  4.上海中医药大学附属第七人民医院肿瘤介入科（上海 200137）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2025.z20250312003
  CLC：
- Received：12 March 2025，
  
  Published：10 December 2025
- 稿件说明：
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朱江川,曹妮达,马芳琪,等.胃肠安调控分化抑制因子1的选择性剪接抑制胃癌细胞恶性进展的机制[J].上海中医药杂志,2025,59(12):70-75.

ZHU Jiangchuan,CAO Nida,MA Fangqi,et al.Mechanism of Weichang'an in inhibiting malignant progression of gastric cancer cells through alternative splicing of inhibitor of differentiation 1[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(12):70-75.
朱江川,曹妮达,马芳琪,等.胃肠安调控分化抑制因子1的选择性剪接抑制胃癌细胞恶性进展的机制[J].上海中医药杂志,2025,59(12):70-75. DOI： 10.16305/j.1007-1334.2025.z20250312003.

ZHU Jiangchuan,CAO Nida,MA Fangqi,et al.Mechanism of Weichang'an in inhibiting malignant progression of gastric cancer cells through alternative splicing of inhibitor of differentiation 1[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(12):70-75. DOI： 10.16305/j.1007-1334.2025.z20250312003.

摘要

目的

探讨健脾中药复方胃肠安（WCA）通过多聚嘧啶结合蛋白3（PTBP3）调控分化抑制因子1（

Id1

）mRNA选择性剪接抑制胃癌细胞恶性进展的作用机制。

方法

利用

PTBP3

基因被稳定沉默的人胃癌细胞MKN45，建立相应的裸小鼠皮下移植瘤模型。模型裸小鼠随机分为MKN45细胞0.9%氯化钠溶液组（NC组，作为对照），MKN45细胞WCA组（NC-WCA组），沉默

PTBP3

MKN45细胞0.9%氯化钠溶液组（shPTBP3组），沉默

PTBP3

MKN45细胞WCA组（shPTBP3-WCA组），每组6只。每日灌胃给予相应干预，共28 d。考察WCA对移植瘤生长、PTBP3及

Id1

异构体表达的影响。采用苏木精-伊红（HE）染色法和Ki67染色法分别观察肿瘤组织形态和肿瘤细胞比例。采用实时荧光定量逆转录聚合酶

链式反应（RT-qPCR）法和Western blot法检测移植瘤细胞内PTBP3、Id1a、Id1b蛋白和mRNA表达。

结果

与NC组相比，NC-WCA组、shPTBP3组、shPTBP3-WCA组小鼠瘤体质量均减轻，差异有统计学意义（

0.05）。HE和Ki67染色提示沉默

PTBP3

和WCA干预均可抑制小鼠MKN45肿瘤细胞增殖能力。RT-qPCR和Western blot结果显示，与NC组相比，沉默

PTBP3

和WCA干预均能使

Id1a

mRNA表达减少，

Id1b

mRNA表达增加，差异均有统计学意义（

0.05）；在沉默

PTBP3

的模型裸小鼠中，WCA干预后

Id1a

mRNA表达减少，

Id1b

mRNA表达增加，差异均有统计学意义（

0.001）；与NC组相比，沉默

PTBP3

和WCA干预均能下调Id1a表达（

0.05），并上调Id1b表达（

0.001），其蛋白表达变化与mRNA表达变化一致。

结论

PTBP3能调控

Id1

异构体的选择性剪接，中药复方WCA通过PTBP3调控

Id1

的选择性剪接，使Id1a表达下调、Id1b表达上调，从而抑制胃癌细胞恶性进展。

Abstract

Objective

To explore the mechanism of strengthening spleen traditional Chinese medicine compound Weichang'an （WCA） in inhibiting malignant progression of gastric cancer cells through polypyrimidine tract-binding protein 3 （PTBP3） regulating alternative splicing of inhibitor of differentiation 1 （

Id1

） mRNA.

Methods

Using the human gastric cell line MKN45 that has been stably silenced for the

PTBP3

gene， a corresponding nude mouse subcutaneous tumor transplantation model was established. The model nude mice were randomly divided into the MKN45 cell 0.9% sodium chloride solution group （NC group， as control）， the MKN45 cell WCA group （NC-WCA group）， the

PTBP3

silenced MKN45 cell 0.9% sodium chloride solution group （shPTBP3 group）， and the

PTBP3

silenced MKN45 cell WCA group （shPTBP3-WCA group）， with 6 mice in each group. The corresponding interventions were administered by intragastric administration daily for a total of 28 d. The effects of WCA on the growth of transplanted tumors， expressions of PTBP3 and

Id1

isomers were investigated. The morphology of the tumor tissue and the proportion of tumor cells were observed by hematoxylin-eosin （HE） staining and Ki67 staining， respectively. Fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR） and Western blot were used to detect the protein and mRNA expression of PTBP3， Id1a and Id1b in transplanted tumor cells.

Results

Compared with the NC group， the tumor weights of mice in the NC-WCA group， the shPTBP3 group， and the shPTBP3-WCA group all decreased， and the differences were statistically significant （

0.05）. The HE and Ki67 staining results indicated that both silencing

PTBP3

and WCA intervention could inhibit the proliferation ability of mouse MKN45 tumor cells. The results of RT-qPCR and Western blot showed that compared with the NC group， both silencing

PTBP3

and WCA intervention could reduce the expression of

Id1a

mRNA and increase the expression of

Id1b

mRNA， and the differences were statistically significant （

0.05）； in the model nude mice with silenced

PTBP3

， after WCA intervention， the expression of

Id1a

mRNA decreased and the expression of

Id1b

mRNA increased， and the differences were statistically significant （

0.001）； compared with the NC group， both silencing

PTBP3

and WCA intervention could down-regulate the expression of Id1a （

0.05） and up-regulate the expression of Id1b （（

0.001）， and the protein expression changes were consistent with the mRNA expression changes.

Conclusions

PTBP3 can regulate the alternative splicing of

Id1

isomers， and the traditional Chinese medicine compound WCA could regulate the alternative splicing of

Id1

through PTBP3， which could down-regulate the e

xpression of Id1a and up-regulate the expression of Id1b， thereby inhibit the malignant progression of gastric cancer cells.

关键词

Keywords

references

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