title: Silencing ADAM10 inhibits the in vitro and in vivo growth of hepatocellular carcinoma cancer cells.
abstract: A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein associated with metastasis in a number of types of cancer. Little is known, however, regarding the role of ADAM10 in hepatocellular carcinoma (HCC). The aim of the present study was to evaluate whether downregulation of ADAM10 effects HCC cell proliferation, cell cycle, cell migration and cell invasion. A recombinant small hairpin RNA expression vector carrying ADAM10 was constructed and then transfected into the HepG2 human HCC cell line. In vitro cell proliferation, cell cycle, cell migration and cell invasion, and in vivo tumor growth were determined following the downregulation of ADAM10 by RNA interference. The results revealed that downregulation of ADAM10 expression in HepG2 tumor cells using the RNA silencing approach significantly suppressed cell proliferation, cell migration and cell invasion in vitro, and tumor growth in vivo. Furthermore, ADAM10 silencing was able to significantly reduce constitutive phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, which implies that ADAM10 is, at least partially, involved in the activation of the PI3K/Akt signaling pathway. These results suggest that ADAM10 is important in regulating the proliferation and metastasis of HCC. Thus, ADAM10 is a promising therapeutic target for the prevention of tumor metastases in HCC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Bai
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human