Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo.
Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo.
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DOI：
10.18632/oncotarget.14811
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发表时间：
2017-02-14
期刊：
影响因子：
--
通讯作者：
Xie M
中科院分区：
文献类型：
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作者：
Cheng H;Lu C;Tang R;Pan Y;Bao S;Qiu Y;Xie M
鞣花酸（EA）是一种在植物和水果中发现的膳食多酚化合物，具有多种药理活性。本研究在体外和体内研究了EA对人胰腺癌PANC-1细胞的影响；并定义了相关的分子机制。体外用CCK-8法和创面愈合法评价细胞生长和修复能力。Tanswell法测定细胞迁移和侵袭活性。在体内，我们用不同浓度的EA处理pach -1细胞荷瘤小鼠，我们发现EA显著抑制细胞生长、细胞修复活性、细胞迁移和侵袭，并呈剂量依赖性。用EA治疗pac -1异种移植小鼠，可显著抑制肿瘤生长，延长小鼠存活率。此外，流式细胞术分析显示，EA增加了细胞周期G1期的细胞百分比。Western blot分析显示，EA可抑制COX-2和NF-κB的表达。此外，EA通过上调E-cadherin和下调Vimentin，逆转上皮细胞向间质细胞的转变。综上所述，本研究表明，EA对细胞生长、细胞修复活性、细胞迁移和侵袭具有剂量依赖性。EA还能有效抑制小鼠胰腺癌的生长。EA的抗肿瘤作用可能与细胞周期阻滞，下调COX-2和NF-κB的表达，通过上调E-cadherin和下调Vimentin逆转上皮向间质转化有关。我们的研究结果表明，EA的使用将有利于胰腺癌的治疗。
Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA. We found that EA significantly inhibited cell growth, cell repairing activity, and cell migration and invasion in a dose-dependent manner. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth and prolong mice survival rate. Furthermore, flow cytometric analysis showed that EA increased the percentage of cells in the G1 phase of cell cycle. Western blot analysis revealed that EA inhibited the expression of COX-2 and NF-κB. In addition, EA reversed epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. In summary, the present study demonstrated that EA inhibited cell growth, cell repairing activity, cell migration and invasion in a dose-dependent manner. EA also effectively inhibit human pancreatic cancer growth in mice. The anti-tumor effect of EA might be related to cell cycle arrest, down-regulating the expression of COX-2 and NF-κB, reversing epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. Our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.