基础医学与临床 ›› 2016, Vol. 36 ›› Issue (9): 1242-1245.

• 研究论文 • 上一篇    下一篇

大黄素通过上调Smad4蛋白表达抑制胰腺癌细胞

肖智伟1,李思源2,谷倬宇3,李军3   

  1. 1. 石河子大学医学院第一附属医院
    2. 石河子大学医学院
    3. 新疆石河子大学医学院第一附属医院
  • 收稿日期:2015-10-22 修回日期:2015-12-26 出版日期:2016-09-05 发布日期:2016-08-30
  • 通讯作者: 李军 E-mail:xjlijun@163.com
  • 基金资助:
    新疆生产建设兵团国际合作基金资助项目

Emodin inhibits pancreatic cancer cells by upregulating the expression of Smad4

  • Received:2015-10-22 Revised:2015-12-26 Online:2016-09-05 Published:2016-08-30

摘要: 目的 以Jab1为作用靶点探讨大黄素抗胰腺癌作用及可能的机制。方法 用免疫印迹实验(Western Blot)法测定胰腺癌PANC-1和AsPC-1细胞系中Jab1与Smad4的蛋白表达。 293T细胞随机分为对照组(不处理)、大黄素组(20μmol/L大黄素处理)、Jab1组(转染HA-Jab1质粒),用免疫共沉淀(IP)测定大黄素组及Jab1对β-TrCP1与Smad4结合的影响。采用Western Blot法检测对照组及大黄素干预组PANC-1和AsPC-1细胞系中Smad4蛋白表达。结果:胰腺癌PANC-1细胞和AsPC-1细胞中Jab1呈高表达,Smad4呈低表达,Jab1与Smad4呈负相关关系(P<0.01)。293T细胞中Jab1 能促使β-TrCP1 与Smad4 结合,促进Smad4蛋白降解;而大黄素通过抑制β-TrCP1 与Smad4 结合,增加Smad4的表达水平(均P<0.05)。结论:与Jab1的作用相反,大黄素可能通过抑制泛素化酶途径,抑制Smad4的降解,从而起到抗肿瘤作用。

关键词: 大黄素, 胰腺癌, 泛素化连接酶, Smad4, Jab1

Abstract: Objective Treat the Jab1 as targets to investigate the effects and possible mechanisms that the emodin effects on the pancreatic cancer cells. Methods Determine the protein expression of Jab1 and Smad4 in the PANC-1 and AsPC-1 cell lines with Western Blot method. The 293T cells were randomly divided into control group (no treatment), emodin group (20μmol / L emodin), Jab1 group (transfected with HA-Jab1 plasmid);Determine the binding between the β-TrCP1 and Smad4 with the IP method in the 293T cells. Determine the level of Smad4 protein expression between control group and emodin group using Western Blot method .Results Jab1 was highly expressed and Smad4 protein expression was low in pancreatic cancer cell lines, both of which were negatively correlated(P<0.05). Jab1 can induce the binding of Smad4 and β-TrCP1 and promote Smad4 protein degradation in the 293T cells; emodin increase the level of Smad4 by inhibiting the binding betweenβ-TrCP1 and Smad4(P<0.05). Conclusion Contract to Jab1, emodin play an anti-tumor role by inhibiting the degradation of Smad4,which is probably by inhibiting ubiquitin pathway enzymes.

Key words: Emodin, Pancreatic cancer, Ubiquitin ligase, Smad4, Jab1

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