牵牛子水煎液对小鼠 H22肝癌皮下移植瘤的抗肿瘤作用和机制
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摘要
[目的]观察牵牛子水煎液对小鼠H22肝癌皮下移植瘤的抗肿瘤作用,分析其可能的抗肿瘤作用机制。[方法]建立小鼠H22肝癌皮下移植肿瘤模型,于肿瘤接种后次日进行随机分组。给药组用牵牛子水煎液4 g/kg进行15 d灌胃治疗,1次/d;模型组用生理盐水灌胃。通过小鼠体质量、自主活动、肿瘤体积、血常规等指标评价牵牛子水煎液对H22肝癌皮下移植瘤小鼠肿瘤生长的抑制作用,利用网络药理学分析牵牛子相关靶点和途径。[结果]模型组小鼠体质量显著上升,自主活动下降,中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)大;与模型组相比,给药组小鼠体质量增加减缓,自主活动增加,中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)小,肿瘤抑制率为33.69%(P<0.05)。网络药理学分析结果筛选出22个牵牛子有效活性成分,PPI网络鉴定了6个核心靶点,涉及30条KEGG通路和29个GO生物过程。[结论]牵牛子水煎液能够抑制小鼠H22肝癌皮下移植瘤的生长,其作用与22个牵牛子活性成分干预TNF信号通路、Toll样受体信号通路、FOXO信号通路、糖酵解或糖异生等途径相关。
[Objective]To observe anti-tumor effect of Semen Pharbitidis decoction on H22 subcutaneously transplanted tumor in mice, and explore its possible action mechanism of action/mode of action. [Methods]The next day after the mouse model of H22 subcutaneously transplanted tumor was established, the tumor bearing mice were randomly divided into two groups; the treatment group and the control group. The mice were treated with Semen Pharbitidis decoction[4 g/kg per mouse]via intragastric administration once-daily for 15 days, the model group received physiological saline. Anti-tumor effect was evaluated by body weight, autonomic activities, tumor size and blood blood routine test. Network network pharmacology was used to analyze the related targets and pathways of Semen Pharbitidis. [Results]Compared with the control group, the Semen Pharbitidis-treated mice had slow body weight increase, increased autonomous activities, increased neutrophils vs lymphocytes and blood platelets vs lymphocytes rate. Compared with the model group, body weight was increased slowly, autonomic activities was increased, rate of neutrophils vs lympocytes and neutrophils vs Platelet was increased in treatment mice, The inhibitory rate of tumor growth was 33.69%(P<0.05). Network pharmacology analysis revealed 22 active components in Semen Pharbitidis, which regulate six core targets Involved in 30 KEGG pathway and 29 GO bioprocess.[Conclusion]Semen Pharbitidis decoction has an inhibitory effect on H22 subcutaneously transplanted tumor in mice, its mechanisms were associated with 22 active components Involved in TNF signaling pathway, Toll-like receptor signaling pathway, FOXO signaling pathway and glycolysis or gluconeogenesis.
[Objective]To observe anti-tumor effect of Semen Pharbitidis decoction on H22 subcutaneously transplanted tumor in mice, and explore its possible action mechanism of action/mode of action. [Methods]The next day after the mouse model of H22 subcutaneously transplanted tumor was established, the tumor bearing mice were randomly divided into two groups; the treatment group and the control group. The mice were treated with Semen Pharbitidis decoction[4 g/kg per mouse]via intragastric administration once-daily for 15 days, the model group received physiological saline. Anti-tumor effect was evaluated by body weight, autonomic activities, tumor size and blood blood routine test. Network network pharmacology was used to analyze the related targets and pathways of Semen Pharbitidis. [Results]Compared with the control group, the Semen Pharbitidis-treated mice had slow body weight increase, increased autonomous activities, increased neutrophils vs lymphocytes and blood platelets vs lymphocytes rate. Compared with the model group, body weight was increased slowly, autonomic activities was increased, rate of neutrophils vs lympocytes and neutrophils vs Platelet was increased in treatment mice, The inhibitory rate of tumor growth was 33.69%(P<0.05). Network pharmacology analysis revealed 22 active components in Semen Pharbitidis, which regulate six core targets Involved in 30 KEGG pathway and 29 GO bioprocess.[Conclusion]Semen Pharbitidis decoction has an inhibitory effect on H22 subcutaneously transplanted tumor in mice, its mechanisms were associated with 22 active components Involved in TNF signaling pathway, Toll-like receptor signaling pathway, FOXO signaling pathway and glycolysis or gluconeogenesis.
引文
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[24] 吴晶晶.G蛋白偶联受体激酶2在肝细胞癌侵袭转移中的作用及其可能机制[D].合肥:安徽医科大学,2014.
[25] 朱倩,卢贵余,桂芬芳,等.TNF-α对肝癌细胞NF-KB信号通路活化的影响及临床意义[J].河北医药,2018,40(24):3700-3703.
[26] 胡杏池,蔡兵.Toll样受体及核转录因子KB信号通路与肝癌发生发展的关系[J].医学综述,2011,17(24):3714-3717.
[27] 陶贵珠,郑洪.FOXO蛋白相关信号通路在卵巢癌发生发展中的作用研究进展[J].山东医药,2018,58(35):93-96.
[28] 郭建路,胡玥,刘闰平,等.细胞色素P450靶向抗肿瘤药物研发进展[J].药学进展,2010,34(7):298-305.
[29] 李博.肿瘤糖代谢紊乱的研究进展和探索[J].中山大学学报(医学科学版),2017,38(2):222-228.
[2] YONG K L,KIM S U,KIM D Y,et al.Prognostic value of α-fetoprotein and des-γ-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization [J].BMC Cancer,2013,13:5.
[3] 黄璐琦.论中药药性理论的研究方向[J].中药与临床,2011,2(2):1-3.
[4] 张丹宇,季宇彬,许旭东,等.牵牛子的化学成分和药理作用研究进展[J].科学技术创新,2018,13(30):13-14.
[5] 辛丹丹.Aglaroxin C对小鼠H22肝癌移植瘤的抑制作用及对其脏器的影响[D].新乡:新乡医学院,2018.
[6] 武容,李晓燕,蔡菲菲,等.基于网络药理学的补肾健脾方治疗肝癌的作用机制研究[J].中华中医药杂志,2018,33(9):4134-4139.
[7] SHANNON P,MARKIEL A,OZIER O,et al.Cytoscape:A software environment for integrated models of biomolecular interaction networks [J].Genome Res,2003,13(11):2498-2504.
[8] 雷奇林,黄雅兰,钟茜,等.基于网络药理学的黄芩抗炎作用机制研究[J].中草药,2018,49(15):3523-3530.
[9] LI Y H,YU C Y,LI X X,et al.Therapeutic target database update 2018:Enriched resource for facilitating benchto-clinic research of targeted therapeutics [J].Nucleic Acid Res,2017,46(1):1121-1127.
[10] JENSEN L J,KUHN M,STARK M,et al.STRING 8-a global view on proteins and their functional interactions in 630 organisms [J].Nucleic Acids Res,2009,37:412-416.
[11] 刘楠,姜云耀,黄婷婷,等.基于网络药理学方法研究补阳还五汤治疗脑梗死的作用机制[J].中国中药杂志,2018,43(11):2190.
[12] 章亮,陈泽慧,陈韩英,等.基于网络药理学的白屈菜抗肿瘤分子机制研究[J].中草药,2018,49(3):646.
[13] 薛潇春,胡晋红.网络药理学的研究方法与应用进展[J].药学实践杂志,2015,33(5):401-405.
[14] ANITHA P,ANBARASU A,RAMAIAH S.Gene network analysis reveals the association of important functional partners involved in antibiotic resistance:a report on an important pathogenic bacterium Staphylococcus aureus[J].Gene,2016,575:253-263.
[15] Hsin K Y,GHOSH S,KITANO H.Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology [J].PLoS ONE,2013,8(12):83922.
[16] 李佳桓.牵牛子酒提取物对Lewis肺癌的抗肿瘤和抗转移机制研究[D].开封:河南大学,2014.
[17] CHEN C L,SONG G Y,XIANG J,et al.AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma[J].Biochemical and Biophysical Research Communications,2017,486(2):514-520.
[18]陆展鹏.基于TCGA数据库肺腺癌相关基因筛选及BUB1BmRNA表达的预后研究[D].南昌:南昌大学,2018.
[19] 王宁,胡莹,高英堂,等.与肝癌浸润相关候选基因的生物信息学分析[J].生物医学工程与临床,2016,20(3):302-308.
[20] 曾洁,邓伟,黄天壬.基于生物信息学途径探究肝细胞癌的关键基因[J].中山大学学报(医学版),2018,39(5):780-790.
[21] 蒲猛,汪建林,黄启科,等.Bub1基因对人肝癌MHCC97-H细胞增殖、周期和凋亡的影响[J].现代生物医学进展,2017,17(12):2201-2204.
[22] LI Y H,BAI W J,ZHANG J J.MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1[J].Biomedicine & pharmacother,2017,92:1038-1044.
[23] 郭梓鑫,晏鑫,李胜,等.基于GEO数据库分析AURKB在膀胱癌中的表达及其临床意义[J].临床肿瘤学杂志,2018,23(8):711-715.
[24] 吴晶晶.G蛋白偶联受体激酶2在肝细胞癌侵袭转移中的作用及其可能机制[D].合肥:安徽医科大学,2014.
[25] 朱倩,卢贵余,桂芬芳,等.TNF-α对肝癌细胞NF-KB信号通路活化的影响及临床意义[J].河北医药,2018,40(24):3700-3703.
[26] 胡杏池,蔡兵.Toll样受体及核转录因子KB信号通路与肝癌发生发展的关系[J].医学综述,2011,17(24):3714-3717.
[27] 陶贵珠,郑洪.FOXO蛋白相关信号通路在卵巢癌发生发展中的作用研究进展[J].山东医药,2018,58(35):93-96.
[28] 郭建路,胡玥,刘闰平,等.细胞色素P450靶向抗肿瘤药物研发进展[J].药学进展,2010,34(7):298-305.
[29] 李博.肿瘤糖代谢紊乱的研究进展和探索[J].中山大学学报(医学科学版),2017,38(2):222-228.
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