基于荷瘤小鼠模型及生物信息学探讨燥湿解毒复方对胰腺癌的影响  

Effect of the compound prescription of detoxication of dryness-dampness on pancreatic cancer based on tumor-bearing mouse model and bioinformatics

作　　者：王小林 雷洋洋 李建柯 高珊珊 蔡定芳[3] WANG Xiao-lin;LEI Yang-yang;LI Jian-ke;GAO Shan-shan;CAI Ding-fang(Department of Interventional Radiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Institute of Medical Imaging,Shanghai 200032,China;Department of Integrative Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院介入治疗科,上海200032 [2]上海市影像医学研究所,上海200032 [3]复旦大学附属中山医院中医-中西医结合科,上海200032

出　　处：《复旦学报（医学版）》2022年第6期916-923,共8页Fudan University Journal of Medical Sciences

基　　金：上海市慈善基金会荣昶专项基金(Q2015-024);复旦大学附属中山医院科研发展基金(2018ZSFZ005)。

摘　　要：目的探讨燥湿解毒复方对小鼠胰腺癌细胞株皮下荷瘤生长的影响,并借助生物信息学判断该燥湿解毒复方治疗胰腺癌的潜在作用机制。方法构建C57BL/6小鼠胰腺癌细胞株皮下荷瘤模型,将40只皮下荷瘤的小鼠随机分为高剂量给药组[27.82 g生药/(kg·d)],中等剂量给药组[13.91 g生药/(kg·d)],低剂量给药组[6.96 g生药/(kg·d)]以及正常对照组(给予磷酸盐缓冲液),每天灌胃1次,共21天。实验过程中观测小鼠体质量变化以及荷瘤体积变化并绘制肿瘤生长曲线,实验结束后测量各组瘤体质量并计算抑瘤率。利用BATMAN-TCM、STRING、GEPIA 2数据库判断该燥湿解毒复方针对胰腺癌的潜在治疗靶点及相关生物学通路,探索靶点分子对胰腺癌患者生存期的影响。结果高剂量给药组和中等剂量给药组的小鼠肿瘤生长曲线较为平稳,低剂量给药组和对照组小鼠的肿瘤生长曲线则相对陡直。实验结束后测量发现高剂量给药组及中等剂量给药组小鼠瘤体质量分别为(0.16±0.08)g及(0.18±0.06)g,明显低于对照组小鼠瘤体质量(P<0.05)。高剂量给药组、中等剂量给药组及低剂量给药组抑瘤率分别为50.00%、43.75%和28.12%(P<0.05)。基于生物信息学分析燥湿解毒复方针对胰腺癌的潜在治疗靶点包括淀粉样前体蛋白(amyloid beta precursor protein,APP)、Polo样激酶1(Polo like kinase 1,PLK1)、过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor gamma,PPARG)、碳酸酐酶2(carbonic anhydrase 2,CA2)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、维甲酸受体β(retinoic acid receptor beta,RARB)、神经降压素受体1(neurotensin receptor 1,NTSR1)和胸苷酸合成酶(thymidylate synthetase,TYMS)。这些靶点蛋白在人体内参与调节骨吸收、细胞对维生素A的反应、星形胶质细胞活化、对超氧阴离子的正向调节、苏氨酸磷酸化的调节、肝细胞再生、一碳代谢过�Objective To investigate the effect of the compound prescription of detoxication of dryness-dampness on the growth of subcutaneous tumor-bearing mouse models with pancreatic cancer cell line,the potential molecular mechanisms by which the compound prescription of detoxication of dryness-dampness treated pancreatic cancer were analyzed by bioinformatics method.Methods The subcutaneous tumor-bearing models with pancreatic cancer cell line were established in C57BL/6 mice.The forty mice were randomly divided into high-dose[27.82 g crude drug/(kg·d)],medium-dose[13.91 g crude drug/(kg·d)],and low-dose[6.96 g crude drug/(kg·d)]groups,as well as control group(treated with phosphate buffered saline).Animals were administered with the Chinese traditional medicine or phosphate buffer solution PBS by gastrogavage,once daily,for 21 days.During the experiment,changes of body weight and tumor volume were observed,and the tumor growth curve was monitored.After the experiment,the tumor weight in each group was measured and the tumor inhibition rate was calculated.Subsequently,the BATMAN-TCM,STRING,and GEPIA 2 databases were utilized to select the potential therapeutic targets and related biological pathways of the compound prescription of detoxication of dryness-dampness for pancreatic cancer,and to explore the effect of target molecules on the survival of pancreatic cancer patients.Results The tumor volume growth curves of the mice with high-or mediumdoses were relatively stable,while changed steeply in low-dose and control groups.Tumor weight levels of mice with high or medium-doses were(0.16±0.08)g or(0.18±0.06)g,respectively,which were significantly lower than that in the control group(P<0.05).Further calculation showed that the tumor inhibition rates were 50.00%,43.75%and 28.12%(P<0.05)at high,medium,or low doses,respectively.Results of bioinformatics analysis showed that amyloid beta precursor protein(APP),Polo like kinase 1(PLK1),peroxisome proliferator activated receptor gamma(PPARG),carbonic anhydrase 2(CA2),epide

关 键 词：燥湿解毒 胰腺癌细胞株 肿瘤生长曲线 抑瘤率 生物信息学 

分 类 号：R273[医药卫生—中西医结合]