基于网络药理学的商陆水煎液治疗小鼠H22肝癌作用机制研究
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摘要
[目的]观察商陆水煎液对小鼠H22肝癌皮下移植瘤生长的抑制作用,并用网络药理学方法探究其抗肿瘤作用机制。[方法]建立小鼠H22肝癌皮下移植肿瘤模型。接瘤后次日,给药组用人体等效日剂量的商陆水煎液1次/d连续灌胃治疗17 d,模型组用等量生理盐水灌胃作对照。通过检测小鼠瘤重和瘤体积等指标,评价商陆水煎液对H22肝癌皮下移植瘤小鼠肿瘤生长的影响。采用网络药理学分析商陆可能的抗肿瘤机制。[结果]与模型组相比,给药组体质量上升相对平缓,自主活动增多;模型组体质量明显上升,自主活动逐渐减少。在肿瘤组织质量方面,给药组与模型组相比有显著性差异(P<0.05)。网络药理学分析结果筛选出20个商陆有效活性成分,涉及33条KEGG通路和27个GO生物过程。[结论]商陆水煎液能够抑制小鼠H22肝癌皮下移植瘤的生长,其作用与20个商陆活性成分干预癌症的途径调节、Jak-STAT信号通路、PI3K-Akt信号通路、癌症中的蛋白多糖的调节、MAPK信号通路、癌症中的微小RNA的调节等途径相关。
[Objective]To observe anti-tumor effect of Shanglu decoction on H22 subcutaneously transplanted tumor in mice, and explore its possible action mechanism with network pharmacology.[Methods]Firstly, a mouse model of H22 subcutaneously transplanted tumor was established, the next day tumor bearing mouse was treated with HED's Shanglu decoction via intragastric administration once a day for 17 days. The model group was given normal saline as control. Antitumor effect was evaluated by body weight, autonomic activities, tumor size and so on, and network pharmacology was used to analyze the related targets and pathways of Shanglu. [Results]Shanglu group compared with model group,Shanglu group's body weight was increased slowly, autonomic activities was increased; model group's body weight was increased fastly, autonomic activities was decreased. The weight of tumor in the model group was lighter than that in the model group(P<0.05). Network pharmacology analysis showed that there are 20 active components in Shanglu, involving in 33 KEGG pathway and 27 GO bioprocess. [Conclusion]Shanglu decoction has an inhibitory effect on H22 subcutaneously transplanted tumor in mice, its mechanisms were associated with 20 active components involving in "Pathways in cancer""Jak-STAT signaling pathway""PI3 K-Akt signaling pathway" "Proteoglycans in cancer""MAPK signaling pathway""MicroRNAs in cancer"and so on.
[Objective]To observe anti-tumor effect of Shanglu decoction on H22 subcutaneously transplanted tumor in mice, and explore its possible action mechanism with network pharmacology.[Methods]Firstly, a mouse model of H22 subcutaneously transplanted tumor was established, the next day tumor bearing mouse was treated with HED's Shanglu decoction via intragastric administration once a day for 17 days. The model group was given normal saline as control. Antitumor effect was evaluated by body weight, autonomic activities, tumor size and so on, and network pharmacology was used to analyze the related targets and pathways of Shanglu. [Results]Shanglu group compared with model group,Shanglu group's body weight was increased slowly, autonomic activities was increased; model group's body weight was increased fastly, autonomic activities was decreased. The weight of tumor in the model group was lighter than that in the model group(P<0.05). Network pharmacology analysis showed that there are 20 active components in Shanglu, involving in 33 KEGG pathway and 27 GO bioprocess. [Conclusion]Shanglu decoction has an inhibitory effect on H22 subcutaneously transplanted tumor in mice, its mechanisms were associated with 20 active components involving in "Pathways in cancer""Jak-STAT signaling pathway""PI3 K-Akt signaling pathway" "Proteoglycans in cancer""MAPK signaling pathway""MicroRNAs in cancer"and so on.
引文
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[11]王欢,谢进,何惠芳,等.茵栀黄颗粒作为肝病辅助用药作用机制的网络药理学研究[J].中国医院用药评价与分析,2016,16(12):1585-1587.
[12]SHI Z,JIANG W,WANG M,et al.Inhibition of JAK/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helpertype 2 cell response in allergic rhinitis[J].Mol Cell Biochem,2017,430(1/2):161-169.
[13]AWAISHEH S S,KHALIFEH M S,Al-RUWAILI M A,et al.Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats[J].Journal of Dairy Science,2013,96(1):9-15.
[14]CáRDENO A,SáNCHEZ-HIDALGO M,Cortes-Delgado A,et al.Mechanisms involved in the antiproliferative and proapoptotic effects of unsaponifiable fraction of extra virgin olive oil on HT-29 cancer cells[J].Nutrition and Cancer,2013,65(6):908-918.
[2]贺珊,廖长秀.中药治疗肝癌机制的研究进展[J].中成药,2017,39(1):155-160.
[3]张家继,李革,李德君.商陆的临床应用[J].中国中医急症2011,20(6):1002.
[4]田普永.商陆的药理作用及临床应用[J].西北药学杂志,1989,10(1):33-35.
[5]范芳芳,郭非非,张雯,等.基于网络药理学的藏药大花红景天抗氧化应激分子机制研究[J].中国中药杂志,2018,43(7):1789.
[6]解世全,罗晶,宋珊珊,等.生附子抗肝肿瘤化学物质组纯化工艺研究[J].时珍国医国药,2016,27(2):300-302.
[7]沈红波,周一农,郑杰,等.基于网络药理学葵花护肝片“多成分-多靶点-多通路”的作用机制研究[J].中国中药杂志,2019,44(7):1464-1474.
[8]SUZUKI T,MIYAMOTO K,YOKOYAMA N,et al.Processed aconite root and its active ingredient neoline may alleviate oxaliplatin-induced peripheral neuropathic pain[J].Journal of ethnopharmacology,2016,10(10):186.
[9]TANAKA Y,NAKAYAMADA S,FUJIMOTO H,et al.H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts[J].Journal of Biological Chemistry,2002,277:21446-21452.
[10]王艳,高斌.JAK-STAT信号通路及STAT蛋白在慢性肝病中的研究进展[J].临床肝胆病杂志,2012,28(11):805-811.
[11]王欢,谢进,何惠芳,等.茵栀黄颗粒作为肝病辅助用药作用机制的网络药理学研究[J].中国医院用药评价与分析,2016,16(12):1585-1587.
[12]SHI Z,JIANG W,WANG M,et al.Inhibition of JAK/STAT pathway restrains TSLP-activated dendritic cells mediated inflammatory T helpertype 2 cell response in allergic rhinitis[J].Mol Cell Biochem,2017,430(1/2):161-169.
[13]AWAISHEH S S,KHALIFEH M S,Al-RUWAILI M A,et al.Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats[J].Journal of Dairy Science,2013,96(1):9-15.
[14]CáRDENO A,SáNCHEZ-HIDALGO M,Cortes-Delgado A,et al.Mechanisms involved in the antiproliferative and proapoptotic effects of unsaponifiable fraction of extra virgin olive oil on HT-29 cancer cells[J].Nutrition and Cancer,2013,65(6):908-918.