Antisense Oligodeoxynucleotides of IGF-II Selectively Inhibit Growth of Human Hepatoma Cells Overproducing IGF-II.

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概要

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• Insulin-like growth factor II (IGF-II) is expressed in many developing embryonic tissues and is involved in mammalian growth and development. After birth, serum IGF-II is mainly produced by liver cells. Many reports have indicated that IGF-II is overexpressed in some hepatocellular carcinoma (HCC) tissue. These findings imply the possible importance of this growth factor in carcinogenesis. We screened four human HCC cell lines and three rat HCC cell lines and found that HuH-7 and HepG2 cells produced fivefold more intracellular IGF-II than the other cell lines. Experimental data indicate that IGF-II functions through the intracrine mode for HuH-7 cells. To study whether the overexpression of IGF-II is significant for the growth of HCC or only a consequence of HCC development, we used antisense oligodeoxynucleotides (ATON) to arrest the translation of IGF-II mRNA, and then measured the effects on cell growth. We found that the production of IGF-II was suppressed by ATON, and the decrease of IGF-II resulted in growth inhibition of HuH-7 and HepG2. ATON had no effect on the other tested cell lines, which produced lower levels of IGF-II. The growth inhibition was mainly attributed to a decrease of cell proliferative activity. The results indicate that the IGF-II-overproducing cell lines do depend on IGF-II for growth, and ATON of IGF-II can selectively inhibit the growth of these cells. ATON may be a potential therapeutic agent for this type of HCC in vivo.

• 社団法人 日本生化学会の論文

著者

• Hsieh Sung-hwa

  Graduate Institute Of Medical Technology National Taiwan University Hospital

• Au Lo-chun

  Department Of Medical Research Veterans General Hospital- Taipei Graduate Institute Of Medical Biote

• Hsu Hui-lun

  Graduate Institute Of Medical Technology National Taiwan University Hospital

• Lin Shwu-bin

  Graduate Institute Of Medical Technology National Taiwan University Hospital

• Kan Lou-sing

  Institute Of Chemistry Academia Sinica

• Lai Ming-yang

  Graduate Institute Of Clinical Medicine College Of Medicine National Taiwan University

• Kan Lou-Sing

  Institute of Chemistry, Academia Sinica, Taipei National Yang-Ming University

関連論文

• Antisense Oligodeoxynucleotides of IGF-II Selectively Inhibit Growth of Human Hepatoma Cells Overproducing IGF-II
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• A Method for Screening Antisense Oligodeoxyribonucleotides Effective for mRNA Translation-Arrest.
• Antisense Oligodeoxynucleotides of IGF-II Selectively Inhibit Growth of Human Hepatoma Cells Overproducing IGF-II.

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