Tianjin Medical Journal

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

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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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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