title: The important role of ADAM8 in the progression of hepatocellular carcinoma induced by diethylnitrosamine in mice.
abstract: This study focuses on investigating the concrete role of a disintegrin and metalloproteinase 8 (ADAM8) in the progression of hepatocellular carcinoma (HCC). Mice received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl, respectively, in phosphate-buffered saline (PBS) or PBS intervention during the progression of HCC induced by diethylnitrosamine. The survival rate, body weight, and relative liver weight were determined in the mice. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and α-fetoprotein (AFP) level, hematoxylin-eosin staining, the expression level of vascular endothelial growth factor A (VEGF-A), proliferating cell nuclear antigen (PCNA), caspase 3 (Casp3), B cell leukemia 2 (Bcl2), B cell leukemia 2-associated X protein (Bax), protein p53 (P53), and ADAM8 were detected in the mice at the end of the 24th week. Our results showed that anti-ADAM8 mAb intervention effectively improved the survival rate, reduced the body weight loss and increased the relative liver weight in mice in a dose-dependent manner (p < 0.05 or p < 0.01). Anti-ADAM8 mAb intervention also significantly lowered serum AST, ALT, and AFP levels (p < 0.05 or p < 0.01), slowed the progression of HCC (p < 0.05 or p < 0.01), induced the expression of Casp3, Bax, and P53 (p < 0.05 or p < 0.01), and inhibited the expression of VEGF-A, PCNA, and Bcl2 in the liver of mice (p < 0.05 or p < 0.01) in a dose-dependent manner compared with the mice receiving PBS intervention. Our study suggested that ADAM8 might promote the progression of HCC by regulating the expression of these factors. Anti-ADAM8 mAb intervention might be suitable as a potential method for HCC therapy.
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China sanqiangli2001@163.com.
authors.forename: S-Q
authors.initials: SQ
authors.lastname: Li
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China.
authors.forename: D-M
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Microbiology Immunology, College of Basic Medical Sciences, Zhengzhou University, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China.
authors.forename: R-F
authors.initials: RF
authors.lastname: Li
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China.
authors.forename: Z-S
authors.initials: ZS
authors.lastname: Xu
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China.
authors.forename: H-M
authors.initials: HM
authors.lastname: Han
mesh_terms: D051722:ADAM Proteins / Q000276:immunology / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004052:Diethylnitrosamine; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494827:Bax protein, mouse; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D051028:bcl-2-Associated X Protein; C467480:vascular endothelial growth factor A, mouse; D004052:Diethylnitrosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D051722:ADAM Proteins; C489402:Adam8 protein, mouse
keywords: ADAM8; Bcl2; HCC; P53; monoclonal antibody