https://scholars.lib.ntu.edu.tw/handle/123456789/522681
標題: | Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-κB signal transduction pathway | 作者: | CHIA-HSIEN CHENG Chou C.H. Kuo M.L. CHANG-YAO HSIEH |
公開日期: | 2006 | 卷: | 25 | 期: | 53 | 起(迄)頁: | 7009-7018 | 來源出版物: | Oncogene | 摘要: | This study is to investigate the molecular mechanism of radiation-enhanced cell invasiveness of hepatocellular carcinoma (HCC) correlating with clinical patients undergoing radiotherapy and subsequently developing metastasis. Three HCC cell lines (HepG2, Hep3B and Huh7) and normal hepatocyte cell line (CL-48) were irradiated with different doses. The effect of radiation on cell invasiveness was determined using the Boyden chamber assay. Radiation-enhanced invasion capability was evident in HCC cells but not in normal hepatocytes. Invasion was observed in gelatin-coated but not fibronectin-coated or type I collagen-coated membranes. Radiation upregulated matrix metalloproteinase-9 (MMP-9) mRNA level, MMP-9 protein level and MMP-9 activity. MMP-9 antisense oligonucleotides inhibited radiation-induced MMP-9 expression and thereby significantly inhibited radiation-induced HCC invasion. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt chemical inhibitors LY294002 and wortmannin suppressed radiation-induced MMP-9 mRNA expression. Transient transfection with dominant-negative Akt plasmid also showed that the PI3K/Akt-signaling pathway was involved in this radiation-induced MMP-9 expression. Moreover, nuclear factor-κB (NF-κB) decoy oligodeoxynucleotide suppressed radiation enhanced MMP-9 promoter activity completely. PI3K/Akt chemical inhibitors inhibited radiation-induced NF-κB-driven luciferase promoter activity. Taken together, our results indicated that sublethal dose of radiation could enhance HCC cell invasiveness by MMP-9 expression through the PI3K/Akt/NF-κB signal transduction pathway. ? 2006 Nature Publishing Group. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33750890673&doi=10.1038%2fsj.onc.1209706&partnerID=40&md5=c85cbbe80528812d61e36007f69e99b9 https://scholars.lib.ntu.edu.tw/handle/123456789/522681 |
ISSN: | 0950-9232 | DOI: | 10.1038/sj.onc.1209706 | SDG/關鍵字: | 2 morpholino 8 phenylchromone; antisense oligonucleotide; collagen type 1; fibronectin; gelatin; gelatinase B; immunoglobulin enhancer binding protein; luciferase; messenger RNA; oligodeoxynucleotide; phosphatidylinositol 3 kinase; protein kinase B; wortmannin; article; cancer invasion; cancer radiotherapy; cell membrane; controlled study; enzyme activity; gene activity; gene expression; genetic transfection; human; human cell; liver carcinogenesis; liver cell; liver cell carcinoma; metastasis; priority journal; promoter region; protein expression; radiation dose; signal transduction; upregulation; 1-Phosphatidylinositol 3-Kinase; Carcinoma, Hepatocellular; Cell Line; Extracellular Matrix; Gene Expression Regulation, Enzymologic; Hepatocytes; Humans; Matrix Metalloproteinase 9; Neoplasm Invasiveness; NF-kappa B; Proto-Oncogene Proteins c-akt; Sensitivity and Specificity; Signal Transduction |
顯示於: | 醫學系 |
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