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反义寡核苷酸对丙型肝炎病毒转染胆管癌细胞的抑制作用 被引量:19

Inhibition of hepatitis C virus (HCV)-transfected cholangiocarcinoma by antisense oligodeoxynucleotides
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摘要 目的 探讨反义寡核苷酸 (ODNs)对丙型肝炎病毒 (HCV)转染胆管癌细胞中HCV的抑制作用。方法 通过半定量逆转录 聚合酶链反应 (RT PCR)检测HCVmRNA表达的变化 ,观察不同浓度 (0~ 6 .0 μmol/L)的HCV核心区ODNs对体外丙肝病毒感染胆管癌细胞 (QBC939)的抑制作用 ;同时以裸鼠为研究对象进一步观察ODNs对HCV的体内抑制作用。结果 ODNs可有效地进入靶细胞在体外与HCV核心基因杂交结合 ,使HCVmRNA的表达明显降低 ,终浓度为 6μmol/L的ODNs作用下无HCVmRNA表达。动物实验观察ODNs组在裸鼠中的瘤体平均直径小于对照组、PBK HCVC转染组 (P <0 .0 1 ) ,成瘤率 2 5 % (5/ 2 0 )低于PBK HCVC转染组 65 % (1 3/2 0 ) (P <0 .0 5) ,成瘤时间 1 5 .3d较对照组 1 2 .0d、PBK HCVC转染组 1 0 .1d延迟 (P <0 .0 1 )。 Objective To study the inhibitory effect of antisense oligodeoxynucleotides (ODNs) on hepatitis C virus (HCV) in cholangiocarcinoma.Methods The QBC939 cells transfected by PBK HCVC, a recombinant HCV containing HCV core gene, were treated by 14 mers ODNs (0 6.0?μmol/L) complementary to HCV core genomic region. With a half ration, the variation of level of HCV mRNA was detected by RT PCR. Moreover, the inhibitory effect of ODNs was observed in nude mice.Results The 14 mers complementary ODNs showed effective inhibition on HCVmRNA and unexpression of HCVmRNA at 6?μmol/L. The mean tumor size of PBK HCVC transfected group and control group were greater than that of ODNs group (P<0.01). Tumors were found at 65% (13/20) and 25% (5/20) among PBK HCVC transfected and ODNs group (P<0.05) respectively. The time of tumor appearance in PBK HCVC transfected group (10.1 days) and control group (12.0 days) were longer than that of ODNs group (15.3 days) (P<0.01).Conclusion A potential therapeutics for ODNs in the treatment of HCV infected cholangiocarcinoma was revealed.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2002年第5期398-400,共3页 Chinese Journal of Experimental Surgery
关键词 抑制作用 胆管癌 丙型肝炎病毒 基因 反义寡核苷酸 Cholangiocarcinoma Hepatitis C virus Gene Oligonucleotide,antisense
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参考文献5

  • 1Ray RB,Meyer K,Ray R,et al.Hepatitis C virus core protein promotes immortalization of primary human hepatocytes[].Journal of Virology.2000
  • 2Lu HY,Michele QY,Swan NT,et al.Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients[].Chinese Medical Journal.2000
  • 3Mizutani T,Kato N,Hirota M,et al.Inhibition of hepatitis C virus replication by antisesse oligonucleotide in culture cells[].Biochemical and Biophysical Research Communications.1995
  • 4Kobayashi M,Ikeda K,Saitoh S,et al.Incidence of primary cholangiocelluar carcinoma of the liver in Japanese with HCV-related cirrhosis[].Cancer.2000
  • 5Goldin RD,Patel NK,Thomas HE.Hepatitis C and bile duct loss[].Journal of Clinical Pathology.1996

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