Moriya K, Matsukura M, Kurokawa K, Koike K
First Department of Internal Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):217-23. doi: 10.1006/bbrc.1996.0038.
While an important goal of treatment for hepatitis B is to prevent the development of hepatocellular carcinoma, there has been no effective therapy for it. Antisense oligodeoxynucleotide treatment could in principle inhibit hepatitis B virus gene expression and suppress tumor development. We used a mouse model for hepatocellular carcinoma, which is transgenic for the hepatitis B virus HBx gene, to study antisense phosphorothioate oligodeoxynucleotides. Among 2 series of sense and antisense oligodeoxynucleotides, only antisense sequences covering the initiation codon of the HBx gene effectively inhibited the expression of the HBx gene in the liver. Intraperitoneal injection of this antisense oligodeoxynucleotide thrice a week for 8 weeks resulted in the prevention of preneoplastic lesion development in the liver without inflammation in the liver or developmental disturbance of the mice. Antisense phosphorothioate oligodeoxynucleotides can inhibit the expression of a hepatitis B virus gene and may be a promising method for the prevention of hepatocellular carcinoma in hepatitis B virus infection.
虽然乙型肝炎治疗的一个重要目标是预防肝细胞癌的发生，但目前尚无有效的治疗方法。反义寡脱氧核苷酸治疗原则上可以抑制乙型肝炎病毒基因表达并抑制肿瘤发展。我们使用了一种肝细胞癌小鼠模型（该模型对乙型肝炎病毒HBx基因进行了转基因）来研究反义硫代磷酸寡脱氧核苷酸。在2系列的正义和反义寡脱氧核苷酸中，只有覆盖HBx基因起始密码子的反义序列能有效抑制肝脏中HBx基因的表达。每周三次腹腔注射这种反义寡脱氧核苷酸，持续8周，可预防肝脏中癌前病变的发展，且肝脏无炎症，小鼠也无发育障碍。反义硫代磷酸寡脱氧核苷酸可以抑制乙型肝炎病毒基因的表达，可能是预防乙型肝炎病毒感染中肝细胞癌的一种有前景的方法。
