中药复方WCAP及拆方对人胰腺癌皮下移植瘤裸小鼠模型及IL⁃6/STAT3信号通路的影响

曹妮达; 李朝燕; 华逢春; 马芳琪; 王强; 高峰; 朱莹杰

doi:10.16305/j.1007-1334.2023.2208046

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中药复方WCAP及拆方对人胰腺癌皮下移植瘤裸小鼠模型及IL⁃6/STAT3信号通路的影响

实验研究 | 更新时间：2023-05-16

- 中药复方WCAP及拆方对人胰腺癌皮下移植瘤裸小鼠模型及IL⁃6/STAT3信号通路的影响
- Effects of traditional Chinese medicine compound formula WCAP and its sub⁃formulas on subcutaneous transplanted tumor nude mouse model of human pancreatic cancer and IL⁃6/STAT3 signaling pathway
- 上海中医药杂志 2023年57卷第5期页码：80-86
- 作者机构：
  
  1.上海中医药大学附属龙华医院肿瘤一科（上海 200032）
  2.上海交通大学医学院附属瑞金医院中医科（上海 200025）
  3.上海中医药大学附属龙华医院核医学科（上海 200032）
- 作者简介：
  
  曹妮达，女，硕士，副主任医师，主要从事中西医结合防治消化道恶性肿瘤研究工作
  高峰，副主任医师，硕士研究生导师； E-mail：gaofenn@sina.com
- 基金信息：
  
  国家自然科学基金项目(82004133);上海市名老中医学术经验研究工作室建设项目(SHGZS-202216);上海中医药大学附属龙华医院龙医学者育苗计划项目(LYTD-44)
- DOI：10.16305/j.1007-1334.2023.2208046
  中图分类号：
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曹妮达,李朝燕,华逢春,等.中药复方WCAP及拆方对人胰腺癌皮下移植瘤裸小鼠模型及IL⁃6/STAT3信号通路的影响[J].上海中医药杂志,2023,57(5):80-86.

CAO Nida,LI Zhaoyan,HUA Fengchun,et al.Effects of traditional Chinese medicine compound formula WCAP and its sub⁃formulas on subcutaneous transplanted tumor nude mouse model of human pancreatic cancer and IL⁃6/STAT3 signaling pathway[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(5):80-86.
曹妮达,李朝燕,华逢春,等.中药复方WCAP及拆方对人胰腺癌皮下移植瘤裸小鼠模型及IL⁃6/STAT3信号通路的影响[J].上海中医药杂志,2023,57(5):80-86. DOI： 10.16305/j.1007-1334.2023.2208046.

CAO Nida,LI Zhaoyan,HUA Fengchun,et al.Effects of traditional Chinese medicine compound formula WCAP and its sub⁃formulas on subcutaneous transplanted tumor nude mouse model of human pancreatic cancer and IL⁃6/STAT3 signaling pathway[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(5):80-86. DOI： 10.16305/j.1007-1334.2023.2208046.

摘要

目的,2,观察中药复方WCAP及其拆方对人胰腺癌BxPC-3细胞裸小鼠皮下移植瘤生长及对白介素-6/信号转导和转录激活因子3（IL-6/STAT3）信号通路的影响。,方法,2,建立人胰腺癌BxPC-3细胞裸小鼠皮下移植瘤模型，将30只SPF级裸小鼠随机分为6组，即空白对照组、5-氟尿嘧啶（5-FU）组、复方组、健脾组、清热解毒组和软坚散结组，每组5只，观察各组裸小鼠皮下移植瘤瘤质量及抑瘤率，实时荧光定量逆转录聚合酶链式反应（RT-qPCR）和Western blot法分别检测瘤组织中IL-6/STAT3通路及其下游靶基因c-myc癌基因（,c,-,myc,）、细胞周期蛋白D1（,cyclin D1,）、血管内皮生长因子（,VEGF,）、基质金属蛋白酶-2（,MMP,-,2,）的mRNA和蛋白表达水平。,结果,2,①与空白对照组比较，各干预组瘤质量均轻于空白对照组，5-FU组、复方组及各拆方组均可抑制裸小鼠皮下移植瘤的生长（,P,<,0.05），复方组抑瘤率高于各拆方组（,P,<,0.05）。②与空白对照组比较，5-FU组、复方组和软坚散结组IL-6/STAT3通路及其下游靶基因,c,-,myc,、,cyclin D1,、,VEGF,、,MMP,-,2,的mRNA表达均降低（,P,<,0.05）。③与空白对照组比较，5-FU组、复方组IL-6/STAT3通路及其下游靶基因涉及的c-myc、cyclin D1、VEGF、MMP-2蛋白表达均降低（,P,<,0.05），软坚散结组c-myc、MMP-2和IL-6蛋白表达均降低（,P,<,0.05）。,结论,2,WCAP复方可抑制人胰腺癌BxPC-3细胞裸小鼠皮下移植瘤的生长，其机制与抑制IL-6/STAT3通路并调节其下游靶基因,c,-,myc,、,cyclin D1,、,VEGF,、,MMP,-,2,的表达水平有关；与各拆方相比，WCAP复方在抑瘤率、小鼠体质量及IL-6/STAT3通路及其下游靶基因调控方面作用更好。

Abstract

Objective,2,To study the effects of traditional Chinese medicine （TCM） compound formula WCAP and its sub-formulas on the tumor growth of subcutaneous transplanted human pancreatic cancer BxPC-3 cells in nude mice and on the interleukin-6/signal transducer and activator transcription 3 （IL-6/STAT3） signaling pathway.,Methods,2,The subcutaneous transplanted tumor model of human pancreatic cancer BxPC-3 cells in nude mice was established. Totally 30 SPF-grade nude mice were randomly divided into 6 groups of 5 mice each， which were blank control group， 5-fluorouracil（5-FU） group， compound group， spleen-invigorating group （SI group）， heat-clearing and toxicity-removing group （HCTR group）， and hardness-resolving group （HR group）. The tumor quality and tumor growth inhibition rate of the subcutaneous transplanted tumor in each group of nude mice were recorded. The mRNA and protein expression levels of IL-6/STAT3 pathway and its downstream target genes ,c,-,myc， cyclin D1， VEGF and MMP,-,2, were detected in tumor tissues by real-time fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR） and Western blot， respectively.,Results,2,①Each intervention group showed lower tumor weight than that of control group. The 5-FU group， compound group and each sub-formula group could inhibit the growth of subcutaneous transplanted tumor in nude mice （,P,<,0.05）， and the tumor growth inhibition rate of the compound group was higher than that of each sub-formula group（,P,<,0.05）. ②The mRNA expression levels of IL-6/STAT3 pathway and its downstream target genes, c,-,myc， cyclin D1， VEGF, and ,MMP,-,2, were lowered in the 5-FU group， compound group and HR group than those in the control group （,P,<,0.05）. ③Compared with those in the control group， the protein expression levels of IL-6/STAT3 pathway and its downstream target genes c-myc， cyclin D1， VEGF， and MMP-2 were lowered in the 5-FU group and compound group （,P,<,0.05）， and the protein expression levels of c-myc， MMP-2， and IL-6 were lowered in HR group （,P,<,0.05）.,Conclusions,2,WCAP compound formula could inhibit the tumor growth of subcutaneous transplanted human pancreatic cancer BxPC-3 cells in nude mice， and the mechanism was related to the inhibition of IL-6/STAT3 pathway and regulation of the expression levels of its downstream target genes ,c,-,myc,， ,cyclin D1,， ,VEGF,， and ,MMP,-,2,. WCAP compound formula showed a better effect on the tumor growth inhibition rate， mouse weight， and IL-6/STAT3 pathway and its downstream target gene regulation than each sub-formula group.

关键词

胰腺癌中药复方白介素-6/信号转导和激活剂转录3信号通路裸小鼠皮下移植瘤模型中药研究

Keywords

pancreatic cancertraditional Chinese medicine compound formulaIL-6/STAT3 pathwaysubcutaneous transplanted tumor model in nude micetraditional Chinese herbal medicine research

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