Suppression of hepatocarcinoma model in vitro and in vivo by ECRG2 delivery using adenoviral vector.
Hepatocarcinoma represents one of the most malignant cancer types. Esophageal cancer-related gene 2 (ECRG2) is found to be critical in the process of carcinogenesis. It regulates urokinase-type plasmin activator receptor and extracellular matrix function and its polymorphism in exon 4 is associated with cancer relapse. To explore new strategies to fight against cancer, here we first systematically evaluated the therapeutic potential as a biological tool using adenoviral vector (Ad-ECRG2). Ad-ECRG2 is exogenously expressed in cytoplasm and is potent to suppress the growth of cancer cell by inducing apoptosis as effective as Ad-p53. Ad-ECRG2 is able to suppress the invasion and adhesion of cancer cells at low titers. It alters the expression of a panel of cancer-related molecules, including nuclear factor-kB, matrix metalloproteinase 2 and E-cadherin, contributing to reverse malignancy phenotype of cancer cells. In vivo experiments show a significant inhibition of cancer growth by intratumoral Ad-ECRG2 administration. No evident toxicity was observed in the model animal during the study. We concluded that ECRG2 is a potential molecular target in biological therapy strategies for cancer treatment.
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China.
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Song
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Song
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Wang
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Li
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Yang
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Lu
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Lin
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Zhan
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Wang
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Qian
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D005822:Genetic Vectors / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061986:MCF-7 Cells; D051379:Mice; D053491:Proteinase Inhibitory Proteins, Secretory / Q000096:biosynthesis / Q000235:genetics*; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays
D053491:Proteinase Inhibitory Proteins, Secretory; C473799:SPINK7 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015842:Serine Proteinase Inhibitors