论著

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 ,
  • 吴志远 ,
  • 王申捷 ,
  • 黄雨晴 ,
  • 李宇熙 ,
  • 郑岚 ,
  • 宁光
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  • 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

  网络出版日期: 2025-04-30

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 ,
  • WU Zhiyuan ,
  • WANG Shenjie ,
  • HUANG Yuqing ,
  • LI Yuxi ,
  • ZHENG Lan ,
  • NING Guang
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  • 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 date: 2024-08-26

  Online published: 2025-04-30

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。

本文引用格式

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 . DOI: 10.16138/j.1673-6087.2025.01.05

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.

参考文献

[1] Liu W, Zhang R, Shu R, et al. Study of the relationship between microbiome and colorectal cancer susceptibility using 16SrRNA sequencing[J]. Biomed Res Int, 2020, 7828392.
[2] Yurgelun MB, Kulke MH, Fuchs CS, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer[J]. J Clin Oncol, 2017, 35(10):1086-1095.
[3] Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(1):17-48.
[4] Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020[J]. Cancer Commun (Lond), 2021, 41(10):1037-1048.
[5] 沈小珩, 周菲. 《伤寒杂病论》对中医治疗肿瘤的临床指导意义[J]. 上海中医药杂志, 2007,(12):47-50.
[6] 应海峰, 张惟郁, 郭元彪, 等. 扶中消积方对胃癌术后化疗患者免疫功能影响的临床观察[J]. 湖南中医药大学学报, 2014, 34(11):43-46.
[7] 郑岚, 吕玲玲, 应海峰, 等. 扶中消积分期疗法治疗直肠癌生存分析[J]. 辽宁中医药大学学报, 2018, 20(1):11-14.
[8] 吕玲玲, 陈敬贤, 武渊, 等. 基于真实世界理论的扶中消积法治疗结直肠癌的生存状况分析及预测[J]. 中国中医药科技, 2022, 29(3):401-404.
[9] 高健, 吴胜男, 王晓静, 等. 基于网络药理学和分子对接技术探讨沙棘活性成分对非酒精性脂肪肝作用机制[J]. 护理研究, 2023, 37(16):2853-2861.
[10] 郭飘婷, 王松坡. 历代中医论治大肠癌[J]. 吉林中医药, 2016, 36(3):223-227.
[11] 陈钰, 何运胜, 赵平武. 中医辨证论治大肠癌的研究进展[J]. 云南中医中药杂志, 2024, 45(3):99-102.
[12] 王皓月, 温俊凯, 孙可向, 等. 范忠泽大肠癌术后中医药分阶段康复治疗策略[J]. 中医药导报, 2025, 31(1):180-184.
[13] 于翔, 张帅林, 刘艺, 等. 白花蛇舌草多糖抗肿瘤作用机制[J]. 河北中医, 2024, 46(10):1752-1754.
[14] 许飞, 李学军. 白术的抗肿瘤作用及临床应用研究进展[J]. 新乡医学院学报, 2021, 38(8):798-801.
[15] 吕俞娇, 周姝婷, 王丽娜, 等. 灵芝活性成分抗肿瘤机制研究进展[J]. 中国临床药理学与治疗学, 2024, 29(8):947-954.
[16] 韩珊珊, 路洋, 刘寨东. 薏苡仁化学成分及抗肿瘤作用研究进展[J]. 中华中医药学刊, 2024, 42(9):210-219.
[17] 黄丽萍, 乔博灵, 颜雪珍, 等. 基于转录组测序及韦恩分析探寻补气中药制剂发挥补气作用的靶基因及其生物学功能[J]. 陕西中医, 2022, 43(1):28-32.
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