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吲哚美辛诱导肝癌细胞凋亡及与环氧合酶-2和凋亡调控基因表达关系 被引量:4

The effects of indomethacin on inducing apoptosis and expression of cyclooxygenase-2 and apoptosis regulating genes in human hepatocellular carcinoma cells
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摘要 目的探讨非甾体类抗炎药(MSAIDs)诱导肝癌细胞株SMMC7721细胞凋亡的作用及可能机制,为其应用于肝细胞癌的化学预防和治疗提供实验和理论依据。方法采用TUNEL法和免疫细胞化学方法研究了不同浓度吲哚美辛对肝癌细胞株SMMC7712的诱导凋亡作用,及其对环氧合酶(COX)2和凋亡相关基因p53、p27kipl、Cmyc蛋白和Fas抗原表达的影响。结果①对照组、100、200、400、600和800μmol/L吲哚美辛组肝癌细胞的细胞凋亡指数分别为(2.4±1.4)%、(4.2±1.5)%、(8.0±3.2)%、(14.3±5.1)%、(14.9±4.3)%和(19.0±6.1)%(P<0.0001)。②对照组、100、200、400、600和800μmol/L吲哚美辛组COX2的表达强度分别为强阳性、强阳性、强阳性、阳性、弱阳性和弱阳性。③对照组、100、200、400、600和800μmol/L吲哚美辛组p27kipl的阳性积分分别为0,3.7±1.4,12.3±2.4,26.3±4.5,44.4±5.1和60.6±7.8(P<0.0001);p53阳性积分分别为5.3±1.2,6.1±2.3,24.1±6.1,46.2±6.9,47.3±6.6和49.0±5.1(P<0.0001);Cmyc的阳性积分分别为5.8±1.6,5.9±1.7,18.6±6.3,22.0±5.6,44.0±8.4,和44.3±6.1(P<0.0001);Fas阳性积分分别为21.7±6.0,24.2±5.5,25.7±5.9,24.3±5.4,23.1±6.6和22.3±4.3(P>0.05)。结论吲哚美辛可诱导肝癌细胞凋亡,且与其? Objective To study the effect of non steroidal anti inflammatory drug(NSAID) on apoptosis of hepatocellular carcinoma (HCC)cell lines(SMMC7721) and explore its anti tumor mechanism. Methods HCC line SMMC7721 was treated with different concentration of indomethacin(IN). Apoptosis was identified by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling(TUNEL)method. The expression of cyclooxygenase (COX) 2,p53,p27 kipl , C myc protein and Fas antigen was identified by immunocytochemical SP staining method. Results ①The apoptosis index was (2.4±1.4)%,(4.2± 1.5)% ,(8.0±3.2)%,(14.3±5.1)%,(14.9±4.3)% and (19.0±6.1)%( P<0.0001 ) in 0,100,200,400,600 and 800 μmol/L of IN groups, respectively. ②Expression intensity of COX 2 was (+++),(+++),(+++),(+++),(++) and (+) in 0,100,200,400,600 and 800 μmol/L of IN groups, respectively. ③ In 0,100,200,400,600 and 800 μmol/L of IN groups, the positive score of p27 kipl were 0, 3.7±1.4,12.3± 2.4 ,26.3±4.5,44.4±5.1 and 60.6±7.8( P<0.0001) respectively. The positive score of p53 was 5.3±1.2,6.1±2.3,24.1±6.1, 46.2 ± 6.9 , 47.3 ± 6.6 and 49.0±5.1 ( P<0.0001) ,respectively. The positive score of c myc was 5.8±1.6,5.9±1.7,18.6±6.3,22.0±5.6,44.0±8.4 and 44.3±6.1( P< 0.0001 ), respectively. The positive score of Fas was 21.7±6.0, 24.2±5.5, 25.7±5.9,24.3±5.4,23.1±6.6 and 22.3±4.3( P>0.05 ). Conclusion IN could induce apoptosis of HCC cell line in vitro by down regulating the expression of COX 2 and up regulating the expression of p27 kipl , p53 and c myc.
出处 《中华消化杂志》 CAS CSCD 北大核心 2004年第10期604-607,共4页 Chinese Journal of Digestion
关键词 吲哚美辛 强阳性 P27KIPL 对照组 肝癌细胞凋亡 诱导 凋亡调控基因 表达 免疫细胞化学方法 环氧合酶 Indomethacin Cyclooxygenase-2 Hepatocallular carcinoma cell Apoptosis
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同被引文献33

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