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Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate

WANG Chun-ting, MENG Mei ZHANG Ji-cheng JIN Chang-jun JIANG Jin-jiao REN Hong-sheng JIANG Jun-mei QIN Cheng-yong YU Dong-qing

中华医学杂志(英文版)2008,Vol.121Issue(17):1707-1711,5.
中华医学杂志(英文版)2008,Vol.121Issue(17):1707-1711,5.

Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate

Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate

WANG Chun-ting, 1MENG Mei 1ZHANG Ji-cheng 1JIN Chang-jun 1JIANG Jin-jiao 1REN Hong-sheng 1JIANG Jun-mei 2QIN Cheng-yong 2YU Dong-qing1

作者信息

  • 1. Department of Medical Intensive Care Unit
  • 2. Department of Digestive Diseases Shandong Province Hospital,Affiliated Hospital of Shandong University,Jinan,Shandong 250021,China
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摘要

Abstract

Background Sodium 4-phenylbutanoate (NaPB) can induce cellular differentiation and cell cycle arrest.However,its potential anticancer properties in hepatocellular carcinoma and influence on normal liver cell are still unclear.We observed the effects of NaPB on growth inhibition,including differentiation and phase growth arrest in normal liver cell line L-02 and hepatocellular carcinoma cell line Bel-7402.Furthermore,we investigated its mechanism in Bel-7402.Methods Hepatocellular carcinoma cells Bel-7402 and normal liver cell line L-02 were treated with NaPB at different concentrations.Light microscopy was used to find morphological change in cells.Cell cycle was detected by flow cytometry.Expression of acetylating histone H4 and of histones deacetylase 4 (HDAC4) were determined by Western blot.The expression of P21WAF1/CIP1 and E-cadherin were observed through immunocytochemistry.Results NaPB treatment led to time dependent growth inhibition in hepatocellular carcinoma cells Bel-7402.NaPB treatment caused a significant decline in the fraction of S phase cells and a significant increase in G0/G1 cells.NaPB increased the expression of P21WAF1/CIP1 and E-cadherin in Bel-7402 and significantly decreased the level of HDAC4 in Bel-7402.NaPB significantly improved the level of acetylating histone H4.The normal liver cell line L-02 showed no distinct changes under treatment with NaPB.Conclusions NaPB inhibited the growth of hepatocellular carcinoma cells Bel-7402 and induced partial differentiation through enhancing the acetylating histones.In Bel-7402,the expressions of P21WAF1/CIP1 and E-cadherin may be related to level of acetylating histones and inhibition of cellular growth.NaPB showed no significant effect on normal liver cells.

关键词

sodium 4-phenylbutyrate/histones/hepatocellular carcinoma/cell line

Key words

sodium 4-phenylbutyrate/histones/hepatocellular carcinoma/cell line

分类

医药卫生

引用本文复制引用

WANG Chun-ting,,MENG Mei,ZHANG Ji-cheng,JIN Chang-jun,JIANG Jin-jiao,REN Hong-sheng,JIANG Jun-mei,QIN Cheng-yong,YU Dong-qing..Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate [J].中华医学杂志(英文版),2008,121(17):1707-1711,5.

基金项目

This research was supported by grants from the Department of Science and Technology of Shandong Province (No.2005GG4402049) and Department of Health of Shandong Province. (No.2005GG4402049)

中华医学杂志(英文版)

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