基于小鼠皮下移植瘤模型探讨扶正消积方的疗效与转录组学特征

doi:10.16138/j.1673-6087.2025.01.05

内科理论与实践 ›› 2025, Vol. 20 ›› Issue (01): 24-29.doi: 10.16138/j.1673-6087.2025.01.05

基于小鼠皮下移植瘤模型探讨扶正消积方的疗效与转录组学特征

吕玲玲^a, 吴志远^b, 王申捷^b, 黄雨晴^a, 李宇熙^a, 郑岚^a, 宁光^c()

上海交通大学医学院附属瑞金医院 a.中医科; b.放射介入科; c.内分泌与代谢科,上海 200025

收稿日期:2024-08-26 出版日期:2025-02-28 发布日期:2025-04-30
通讯作者: 宁光 E-mail:ng10679@rjh.com.cn
基金资助:
国家自然科学基金青年项目(82305345)

Study on efficacy and transcriptomics characteristics of Fuzheng Xiaoji recipe based on subcutaneous transplanted tumor model in mice

LYU Lingling^a, WU Zhiyuan^b, WANG Shenjie^b, HUANG Yuqing^a, LI Yuxi^a, ZHENG Lan^a, NING Guang^c()

a. Department of Traditional Chinese Medicine; b. Department of Interventional Radiology; c. Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2024-08-26 Online:2025-02-28 Published:2025-04-30
Contact: NING Guang E-mail:ng10679@rjh.com.cn

摘要/Abstract

摘要：

目的：基于小鼠皮下移植瘤模型，探讨扶正消积方治疗结直肠癌的有效性和安全性。方法：构建皮下移植瘤小鼠模型，应用高通量转录组测序技术，扶正消积方治疗后，通过Ensembl数据库、基因本体 (gene ontology，GO)及京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）进行基因注释，对比分析差异表达基因的生物学功能。苏木精-伊红（hematoxylin and eosin，HE）染色法观察中药扶正消积方对小鼠肝、肾组织的影响。结果：扶正消积方低剂量组和高剂量组肿瘤大小和重量均显著低于对照组（P<0.001）。扶正消积方治疗后小鼠肿瘤组织中上调基因166个，下调基因328个。KEGG通路分析显示，在P<0.05条件下前20条代谢通路富集在钙信号通路、环磷酸鸟苷-蛋白激酶G信号通路、环磷酸腺苷信号通路等。HE染色结果显示，扶正消积方处理后的小鼠组织并未观察到明显肝肾毒性。结论：扶正消积方可剂量依赖性地抑制CT26皮下移植瘤生长，且未表现明显肝肾毒性，其可能通过调控结直肠癌细胞增殖，诱导凋亡，抑制肿瘤迁移和侵袭相关。

关键词: 中医药, 结直肠癌, 皮下移植瘤小鼠, 转录组学分析, 扶正消积方

Abstract:

Objective To explore the efficacy and safety of Fuzheng Xiaoji recipe in the treatment of colorectal cancer based on the subcutaneous transplanted tumor model in mice. Methods The subcutaneous tumor transplantation mouse model was established and the mice received Fuzheng Xiaoji recipe treatment, which could strengthen the body resistance and eliminate stagnation. The high-throughput transcriptome sequencing technology was used to evaluate treatment effect. The differentially expressed genes were annotated through Ensembl, gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and the related biological functions of abnormally expressed genes were compared and analyzed. Hematonylin and eosin （HE) staining was used to observe the effect of Fuzheng Xiaoji recipe on liver and kidney of tumor-bearing mice. Results Tumor volume and weight in both the low-dose and high-dose groups of Fuzheng Xiaoji treatment were significantly lower than those in the control group (P<0.001). Transcriptomic analysis revealed 166 upregulated and 328 downregulated genes in the tumor tissues after Fuzheng Xiaoji recipe treatment. Hierarchical clustering analysis, based on transcripts per million (TPM) values, demonstrated significant differences in gene expression between the treatment group and control groups. KEGG pathway analysis indicated that the top 20 enriched metabolic pathways included the calcium signaling pathway, cyclic guanosine monophosphate (cGMP)-protein kinase G signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway (P<0.05). HE staining results showed there were no significant hepatotoxicity or nephrotoxicity in Fuzheng Xiaoji recipe treated mice. Conclusions Fuzheng Xiaoji recipe could reduce the growth of CT26 subcutaneous transplanted tumors in a dose-dependent manner in mice, and it didn’t show obvious hepatorenal toxicity. Transcriptome analysis showed that the therapeutic effect of Fuzheng Xiaoji recipe on colorectal cancer may relate to regulating the proliferation of colorectal cancer, inducing apoptosis of colorectal cancer cells and inhibiting tumor migration and invasion.

Key words: Traditional Chinese medicine, Colorectal cancer, Subcutaneous transplanted tumor mice, Transcriptome analysis, Fuzheng Xiaoji recipe

中图分类号:

R735

吕玲玲, 吴志远, 王申捷, 黄雨晴, 李宇熙, 郑岚, 宁光. 基于小鼠皮下移植瘤模型探讨扶正消积方的疗效与转录组学特征[J]. 内科理论与实践, 2025, 20(01): 24-29.

LYU Lingling, WU Zhiyuan, WANG Shenjie, HUANG Yuqing, LI Yuxi, ZHENG Lan, NING Guang. Study on efficacy and transcriptomics characteristics of Fuzheng Xiaoji recipe based on subcutaneous transplanted tumor model in mice[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(01): 24-29.

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时间	对照组	扶正消积方低剂量组	扶正消积方高剂量组
第0天	17.80±0.57	17.45±0.31	17.55±0.68
第5天	18.15±0.19	18.06±0.27	18.33±0.30
第10天	18.38±0.50	18.41±0.25	18.51±0.43
第15天	18.75±0.27	18.96±0.63	19.03±0.59

基于小鼠皮下移植瘤模型探讨扶正消积方的疗效与转录组学特征

Study on efficacy and transcriptomics characteristics of Fuzheng Xiaoji recipe based on subcutaneous transplanted tumor model in mice

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