天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (8): 1319-1324.doi: 10.16333/j.1001-6880.2018.8.006

• 研究论文 • 上一篇    下一篇

除痰解毒方联合吉非替尼对肺腺癌H1975荷瘤小鼠Twist、Fibronectin表达的影响

罗杨1,2,王淑美1,2*,童冰杰1,2,赵宾1,2,刘启欧1,2,魏玉林1,2   

  1. 1重庆医科大学中医药学院; 2中医药防治代谢性疾病重庆市重点实验室 重庆 400016
  • 出版日期:2018-09-04 发布日期:2018-09-04
  • 基金资助:

    国家中医药管理局课题JDZX2015073;重庆市卫生局课题(2017-38,ZY201702131)

Effects of Chutan Jiedu Decoction Combined with Gefitinib on the Expressions of Twist and Fibronectin in Nude Mouse Xenografts Models of H1975 Human Lung Adenocarcinoma

LUO Yang1,2,WANG Shu-mei1,2*,TONG Bing-jie1,2,ZHAO Bin1,2,LIU Qi-ou1,2,WEI Yu-lin1,2   

  1. 1Department of Traditional Chinese Medicine,Chongqing Medical University; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases Chongqing 400016,China
  • Online:2018-09-04 Published:2018-09-04

摘要: 本文研究除痰解毒方(Chutan Jiedu Decoction,CJD)联合吉非替尼对肺腺癌 H1975 荷瘤小鼠移植瘤twist、fibronectin表达的影响,从上皮间质转化(Epithelial-mesenchymal transition,EMT)角度探讨其抗肿瘤作用机制。建立人肺腺癌H1975耐药细胞荷瘤裸鼠模型,随机分为模型组,吉非替尼组,除痰解毒方低、中、高剂量组,除痰解毒方中剂量联合吉非替尼组,每组10 只,各组予以相应的药物灌胃2周。检测瘤体积和瘤质量,计算抑瘤率,采用免疫组织化学法、Western blot法、荧光定量 PCR法检测各组肿瘤组织twist、fibronectin蛋白及基因的表达。结果显示,联合用药组抑瘤率为61.92%,明显高于模型组、吉非替尼组,除痰解毒方低、中、高剂量组(P<0.01)。免疫组织化学法、Western blot法及荧光定量PCR法结果均显示除痰解毒方中剂量、高剂量及联合用药组均能下调twist和fibronectin的表达,且联合用药组下调作用高于单独用药组(P<0.01)。研究结果表明除痰解毒方联合吉非替尼对肺腺癌 H1975 荷瘤小鼠移植瘤生长及twist、fibronectin表达的抑制作用优于除痰解毒方单药及吉非替尼组, 其协同增效作用可能与逆转EMT增强吉非替尼的敏感性有关。

关键词: 除痰解毒方, 肺癌, H1975, twist, fibronectin

Abstract: The objective of this study was to investigate the effects of CJD combined with Gefitinib on the protein expressions of twist,fibronectin and their mRNA in nude mouse xenografts models of H1975 human lung and to study its anti-tumor mechanisms from EMT.60 BALB/c mice were selected to establish lung cancer xenograft models with lung adenocarcinoma H1975 drug-resistant cells,which were randomly divided into six groups (n=10):control group,Gefitinib-treated group,CJD low-dose group,CJD middle-dose group,CJD high-dose group,and the combined medication group (CJD + Gefitinib-treated).Mice in each group were given intragastric administration with corresponding drugs for 2 weeks.The tumor size and tumor weight were detected.And the tumor inhibitory rates were calculated.The protein expressions of twist,fibronectin and their mRNA were detected by methods of immunohistochemistry,Western blotting and real-time PCR.Result:The tumor inhibitory rates of the combined medication group was 61.92%,which was higher than that of the control group,Gefitinib-treated group,CJD low-dose group,CJD middle-dose group and CJD high-dose group (P<0.01).The results of immunohistochemistry,Western blotting and Real-time PCR showed that the expressions of twist and fibronectin proteins and mRNA in CJD middle-dose group,CJD high-dose group and the combined medication group decreased significantly.And the combined medication group decreased than that of CJD or gefitinib alone(P<0.01).The inhibitory effect of CJD combined with gefitinib on the growth of the lung adenocarcinoma H1975 xenograft in nude mice and the protein and mRNA expression levels of twist and fibronectin is superior to that of CJD or gefitinib alone.The combination of the two can play a synergistic effect,and its possible mechanism maybe related to reverse EMT to enhance the sensitivity of gefitinib.

Key words: Chutan Jiedu Decoction, lung cancer, H1975, twist, fibronectin  

中图分类号: 

R271.19