天津医药

天津医药 ›› 2014, Vol. 42 ›› Issue (12): 1159-1162.doi: 10.3969/j.issn.0253-9896.2014.12.003

• 细胞与分子生物学 • 上一篇    下一篇

姜黄素的抗胰腺癌作用及相关机制研究

谷倬宇1,李思源1,肖智伟1,周婷2,李军1   

  1. 1. 新疆石河子大学医学院, 新疆地方与民族高发病教育部重点实验室
    2. 石河子大学医学院第一附属医院中心实验室
  • 收稿日期:2014-05-07 修回日期:2014-08-13 出版日期:2014-12-15 发布日期:2014-12-15
  • 通讯作者: 李军 E-mail:xjlijun@163.com
  • 基金资助:
    抑癌基因Smad4-Jab1与胰腺癌发生发展关系的合作研究

The Anti-Tumor Effect and Mechanism of Curcumin in Pancreatic Cancer

GU Zhuoyu 1,LI Siyuan 2,XIAO Zhiwei 1, ZHOU Ting 3,LI Jun 1   

  1. 1. First Affiliated Hospital, Medical College of Shihezi University, Shihezi 832002, China; Medical College of Shihezi
    2. Medical College of ShiheziUniversity, Key Laboratory of Ministry of Education, Xinjiang Endemic and Ethnic Diseases
    3. First Affiliated Hospital, Medical College of Shihezi University, Shihezi 832002, China;
  • Received:2014-05-07 Revised:2014-08-13 Published:2014-12-15 Online:2014-12-15
  • Contact: LI Jun E-mail:xjlijun@163.com

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摘要：

【摘要】 目的 探讨姜黄素(curcumin)的抗胰腺癌作用及其可能的机制。 方法 采用免疫组化法检测 35 例胰腺癌组织及相邻非癌组织中 Smad4、Jab1 的表达情况， 并从中抽取 21 例胰腺癌组织测定 Jab1 与 Smad4 染色的阳性细胞百分比， 分析两者相关性。 将人胰腺癌细胞系 PANC-1 细胞分为 PANC-1 对照组（不做处理）和 PANC-1 cur? cumin 组（含 10 μmol/L 姜黄素的细胞培养液处理）， 采用 Western Blot 检测姜黄素对肿瘤抑制物 p53、Smad4 及细胞循环抑制剂 p27 蛋白表达的影响。 将人胚肾细胞系 293T 细胞分为 293T 对照组（不做处理）、293T curcumin 组（含 10 μmol/L 姜黄素的细胞培养液处理）和 293T Jab1 组（ 转染 HA-Jab1 质粒）， 采用免疫共沉淀法检测姜黄素对β- TrCP1 与 Smad4 结合的蛋白表达影响。 结果 与相邻非癌组织比较， 胰腺癌组织中 Smad4 呈低表达， Jab1 呈高表达（均 P＜ 0.01）， Jab1 与 Smad4 的表达呈负相关(n=21， r=-0.71， P=0.007)。 姜黄素可增加 PANC-1 细胞中 Smad4、p53 和 p27 蛋白表达的水平， 降低 293T 细胞中β-TrCP1 与 Smad4 结合的蛋白表达水平； Jab1 可增加 293T 细胞中β- TrCP1 与 Smad4 结合的蛋白表达水平（均 P＜ 0.05）。 结论 姜黄素可能通过上调 Smad4、p53 和 p27 的蛋白表达进而起到抗胰腺癌作用， 其上调 Smad4 表达的机制可能与其抑制 Smad4 蛋白的泛素化进程有关， 而 Jab1 也可能通过参与 Smad4 的泛素化进程影响 Smad4 蛋白降解。

关键词: 胰腺肿瘤, 姜黄素, Smad4蛋白质, 肿瘤抑制蛋白质p53, 周期素依赖激酶抑制剂p27, 泛素化, Jab1

Abstract:

[Abstract] Objective To investigate the anti-tumor effect and mechanism of curcumin in pancreatic cancer (PC). Methods Smad4 and Jab1 expressions were detected by immunohistochemistry in tumor tissues and pericarcinomatous tis? sue from 35 PC cases, and the correlation of Smad4 and Jab1 were analyzed based on the percentage of positive staining in? tissues from 21 random selected PC cases. The effect of curcumin on expressions of tumor suppressors p53, Smad4 and cell cycle inhibitor p27 were examined by Western Blotting after human pancreatic cancer cell line PANC-1 were divided into PANC-1 control group (no treatments were given) and PANC-1 curcumin group (treated with cell culture medium containing 10 μmol/L curcumin). The effect of curcumin on expressions of combination of β-TrCP1 and Smad4 was examined by CoImmunoprecipitation after human embryonic kidney cell line 293T were divided into 293T control group (no treatments were given), 293T curcumin group (treated with cell culture medium containing 10 μmol/L curcumin) and 293T Jab1 group (trans? fected by HA-Jab1 plasmid). Results Compared with expressions in pericarcinomatous tissues, Smad4 was down regulated while the expression of Jab1 was upregulated in PC tissues (P < 0.01), and the expression of Smad4 was negatively correlated with the expression of Jab1 (n=21, r=-0.71, P=0.007). After treated with curcumin, the protein expression of p53, Smad4and and p27 was increased in PANC1 cell, and the protein expression of the combination of β-TrCP1 and Smad4 was decreased in 293T cell (P < 0.05). After transfected by HA-Jab1 plasmid, the protein expression of the combination of β-TrCP1 and Smad4 was increased in 293T cell (P < 0.05). Conclusion Curcumin may have suppression effect of PC through increasing the protein expression of p53, Smad4 and p27, and the mechanism of Smad4 upregulation may be related with the inhibition of Smad4 ubiquitination process, while Jab1 may be also involved in Smad4 degradation through ubiquitination.

Key words: pancreatic neoplasms, curcumin, Smad4 protein, tumor suppressor protein p53, cyclin-dependent kinase inhibitor p27, ubiquitination, Jab1