Chen Na-Na, Wu Shu-Guang
College of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jun;26(6):814-7.
To investigate the effects of cyclooxygenase inhibitor diclofenac on the proliferation and cyclooxygenase-2 (COX-2) mRNA expression of cultured hepatocellular carcinoma cell lines HepG2, Hep3B and human hepatocellular cell line QSG-7701.
After exposure to diclofenac at various concentrations (10-200 micromol/L) for 24, 48 and 72 h, the cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay and mRNA expression determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).
Diclofenac exposure for 24, 48 and 72 h significantly inhibited HepG2 and Hep3B cell proliferation in a concentration-dependent manner, with inhibition rate of 40.47% and 54.49% after 48 h exposure to 50 micromol/L diclofenac and IC50 of 70.54 and 48.39 micromol/L, respectively. A much weaker antiproliferative effect on QSG-7701 cells was shown, with IC50 of 189.91 micromol/L after 48-hour exposure to diclofenac. RT-PCR detected COX-2 mRNA in HepG2 and Hep3B cells, but hardly in QSG-7701 cells. Treatment with diclofenac or 5-Fu resulted in elevated COX-2 mRNA expression both in HepG2 and Hep3B cells.
Diclofenac can specifically inhibit the proliferation of COX-2-expressing HepG2 and Hep3B cells, and induce up-regulation of COX-2 mRNA expression, which indicates the important role of COX-2 in the proliferation of hepatoma cells.
研究环氧化酶抑制剂双氯芬酸对培养的肝癌细胞系HepG2、Hep3B及人肝细胞系QSG - 7701增殖和环氧化酶 - 2(COX - 2)mRNA表达的影响。
将细胞分别暴露于不同浓度(10 - 200 μmol/L)双氯芬酸中24、48和72小时后,采用细胞计数试剂盒 - 8(CCK - 8)法分析细胞增殖情况,并用半定量逆转录 - 聚合酶链反应(RT - PCR)检测mRNA表达。
双氯芬酸作用24、48和72小时后,均以浓度依赖方式显著抑制HepG2和Hep3B细胞增殖,50 μmol/L双氯芬酸作用48小时后抑制率分别为40.47%和54.49%,IC50分别为70.54和48.39 μmol/L。双氯芬酸对QSG - 7701细胞的抗增殖作用较弱,48小时暴露后的IC50为189.91 μmol/L。RT - PCR检测到HepG2和Hep3B细胞中有COX - 2 mRNA表达,而QSG - 7701细胞中几乎未检测到。双氯芬酸或5 - 氟尿嘧啶处理后,HepG2和Hep3B细胞中COX - 2 mRNA表达均升高。
双氯芬酸可特异性抑制表达COX - 2的HepG2和Hep3B细胞增殖,并诱导COX - 2 mRNA表达上调,这表明COX - 2在肝癌细胞增殖中起重要作用。