title: Synergistic effects of co-expression plasmid‑based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo.
abstract: A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to correlate with hepatocellular carcinoma (HCC) grade and clinical outcome and its potential as a target for HCC therapy has been established. Gene associated with retinoid-interferon-induced mortality 19 (GRIM-19), a signal transducer and activator of transcription 3 (Stat3)-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. In the present study, we investigated whether a combined treatment with ADAM10-specific siRNA and GRIM19 gene could have an enhanced anticancer effectiveness on HCC in vitro and in vivo. We developed a dual expression plasmid that co-expressed ADAM10-specific siRNA and GRIM19, to evaluate its effects on HCC growth. Our results showed that simultaneous expression of ADAM10-specific siRNA and GRIM19 (pSi-ADAM10-GRIM19) in HepG2 cancer cells significantly inhibited the proliferation, migration and invasion, and induced cell apoptosis in vitro, and it also suppressed tumor growth in a nude mouse model when compared to the controls, either ADAM10-specific siRNA or GRIM-19 alone. In summary, our data demonstrated that a combined strategy of co-expressed ADAM10-specific siRNA and GRIM19 synergistically and more effectively suppressed HCC tumor growth, and has therapeutic potential for the treatment of HCC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, 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, 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, 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, P.R. China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The First Hospital, Jilin University, Changchun, Jilin, 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, P.R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human