摘要: |
[目的] 通过网络药理学预测和动物实验验证,确证逍遥散干预结肠癌肝转移的作用及信号通路。[方法] 通过网络数据库筛选逍遥散化学成分与结肠癌肝转移相关基因,构建逍遥散干预结肠癌肝转移的蛋白互作网络,对交集基因进行基因本体(GO)分类富集分析和京都基因与基因组百科全书(KEGG)富集分析。建立结肠癌肝转移动物模型,逍遥散给药后观察记录脾脏、肝脏表面癌结节数及腹腔受累情况;肝脏病理切片苏木精-伊红(HE)染色检测癌细胞和炎性细胞浸润情况;肝组织蛋白免疫印迹(Western Blot)检测靶点蛋白表达水平。[结果] 网络数据库筛选出逍遥散干预结肠癌肝转移的178个靶点,GO分析结果显示多集中在DNA结合转录因子结合、细胞因子受体结合、泛素样蛋白连接酶结合上,KEGG富集主要信号通路包括动脉粥样硬化、晚期糖基化终末产物(AGE)-受体(RAGE)信号通路、肝炎等,原癌基因c-jun(JUN)、信号传导转录激活因子3(Stat3)、丝氨酸/苏氨酸蛋白激酶(Akt1)是其发挥作用的主要靶点。动物实验发现逍遥散能减少结肠癌肝转移小鼠脾脏和肝脏表面转移癌结节数,HE染色显示逍遥散能减少肝脏炎性细胞和肿瘤细胞浸润,Western Blot结果显示逍遥散能抑制c-Jun、Stat3、c-Jun氨基末端激酶(JNK)蛋白的磷酸化表达水平。[结论] 网络药理学及实验验证确证了逍遥散阻延结肠癌肝转移肿瘤生长的作用,其作用机制与调控JNK信号通路有关。 |
关键词: 逍遥散 肝脾同病 结肠癌肝转移 网络药理学 |
DOI:10.11656/j.issn.1672-1519.2024.12.20 |
分类号:R735.35 |
基金项目:四川省科技厅自然科学基金项目(2023NSFSC1809)。 |
|
Study on the effect and mechanism of Xiaoyao Powder in treating liver metastasis of colon cancer based on network pharmacology and experimental verification |
CHENG Yuan1, TANG Yi1, WANG Qiaoling2, YUAN Qianghua3
|
1.Sichuan Key Laboratory of Traditional Chinese Medicine Regulation of Metabolic Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;2.Research Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;3.Department of Pharmacy, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
|
Abstract: |
[Objective] To confirm the effect of Xiaoyao Powder on hepatic metastasis of colon cancer and its signaling pathway through network pharmacological prediction and animal experiments. [Methods] The chemical components of Xiaoyao Powder and genes related to liver metastasis of colon cancer were screened through the network database,and the protein interaction network of Xiaoyao Powder was constructed to interfere with liver metastasis of colon cancer. GO function and KEGG enrichment of the intersection genes were analyzed. The animal model of liver metastasis of colon cancer was established. The number of nodules on the surface of spleen and liver was recorded after Xiaoyao Powder was administered. The infiltration of cancer cells and inflammatory cells was detected by HE staining. The expression level of the target protein was detected by Western Blot. [Results] The 178 targets were screened of Xiaoyao Powder for the intervention of colon cancer liver metastasis. GO analysis results showed that most of the targets were DNA binding,transcription factor binding,cytokine receptor binding,and ubiquitin-like protein ligase binding. The main signaling pathways of KEGG enrichment included atherosclerosis,diabetes-related AGE-RAGE signaling pathway,hepatitis,etc. Jun,Stat3,and Akt1 are the main targets of its action. Animal experiments showed that Xiaoyao Powder could reduce the number of metastatic cancer nodules on the spleen and liver surface in mice. HE staining showed that Xiaoyao Powder could reduce the infiltration of liver inflammatory cells and tumor cells,and Western blot showed that Xiaoyao Powder could inhibit the phosphorylation of c-Jun,Stat3,and JNK proteins. [Conclusion] The effect of Xiaoyao Powder on inhibiting the growth of colon cancer liver metastases was confirmed by network pharmacology and experimental verification,and its mechanism is related to regulating the JNK signaling pathway. |
Key words: Xiaoyao Powder simultaneous disease of liver and spleen liver metastasis of colon cancer network pharmacology |