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全反式维甲酸对胰腺癌细胞细胞周期及碱性磷酸酶活性的影响。

The effects of all-trans-retinoic acid on cell cycle and alkaline phosphatase activity in pancreatic cancer cells.

作者信息

Guo J M, Xiao B X, Lou Y R, Wang D H, Yan C H, Zhan L, Zhao W H

机构信息

Ningbo University School of Medicine, Ningbo 315211, China.

出版信息

Med Chem. 2006 Sep;2(5):457-61. doi: 10.2174/157340606778250298.

Abstract

Pancreatic cancer is one of the tumors with the highest mortality, poorly responding to available chemotherapeutic agents. The objective of this study was to study the anticancer effects of all-trans retinoid acid, a functional form of vitamin A, on pancreatic cancer cells. Human pancreatic cancer MiaPaCa-2 cells were treated with 1, 5, 10, 20, 30, 40 and 50 microM ATRA for 1, 2, 3, 4, 5 or 6 d, respectively. Cell growth was determined by MTT viability assay. The cell cycle distribution and the alkaline phosphatase (ALP) activity were analyzed by flow cytometry and chemical analyzer, respectively. The results show that ATRA significantly inhibited the growth of MiaPaCa-2 cells at 40 and 50 microM. ATRA arrested pancreatic cancer cells at G0/G1 phase. The sub-G1 peak and DNA fragmentation were observed. There were time and dose dependent increases in alkaline phosphatase activity (ALP), an indicator of cell differentiation, upon treatment with ATRA when compared to controls. In conclusion, ATRA has an inhibitory effect on the cell growth of MiaPaCa-2, and its tumor suppressive effect is by means of cell cycle arrest and apoptosis induction.

摘要

胰腺癌是死亡率最高的肿瘤之一,对现有的化疗药物反应不佳。本研究的目的是研究维生素A的一种功能形式——全反式维甲酸对胰腺癌细胞的抗癌作用。分别用1、5、10、20、30、40和50微摩尔的全反式维甲酸处理人胰腺癌细胞MiaPaCa-2细胞1、2、3、4、5或6天。通过MTT活力测定法测定细胞生长情况。分别通过流式细胞术和化学分析仪分析细胞周期分布和碱性磷酸酶(ALP)活性。结果表明,40和50微摩尔的全反式维甲酸显著抑制了MiaPaCa-2细胞的生长。全反式维甲酸使胰腺癌细胞停滞于G0/G1期。观察到亚G1峰和DNA片段化。与对照组相比,用全反式维甲酸处理后,作为细胞分化指标的碱性磷酸酶活性(ALP)呈时间和剂量依赖性增加。总之,全反式维甲酸对MiaPaCa-2细胞的生长具有抑制作用,其肿瘤抑制作用是通过细胞周期停滞和诱导凋亡实现的。

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