https://scholars.lib.ntu.edu.tw/handle/123456789/502684
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | DA-LIANG OU | en_US |
dc.contributor.author | Lee B.-S. | en_US |
dc.contributor.author | LIANG-IN LIN | en_US |
dc.contributor.author | Liou J.-Y. | en_US |
dc.contributor.author | Liao S.-C. | en_US |
dc.contributor.author | CHIUN HSU | en_US |
dc.contributor.author | ANN-LII CHENG | en_US |
dc.creator | Cheng A.-L.;Hsu C.;Liao S.-C.;Liou J.-Y.;LIANG-IN LIN;Lee B.-S.;Ou D.-L. | - |
dc.date.accessioned | 2020-06-16T07:53:34Z | - |
dc.date.available | 2020-06-16T07:53:34Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/502684 | - |
dc.description.abstract | Background: To explore whether combining inhibitors that target the insulin-like growth factor receptor (IGFR)/PI3K/Akt/mTOR signaling pathway (vertical blockade) can improve treatment efficacy for hepatocellular carcinoma (HCC).Methods: HCC cell lines (including Hep3B, Huh7, and PLC5) and HUVECs (human umbilical venous endothelial cells) were tested. The molecular targeting therapy agents tested included NVP-AEW541 (IGFR kinase inhibitor), MK2206 (Akt inhibitor), BEZ235 (PI3K/mTOR inhibitor), and RAD001 (mTOR inhibitor). Potential synergistic antitumor effects were tested by median dose-effect analysis in vitro and by xenograft HCC models. Apoptosis was analyzed by flow cytometry (sub-G1 fraction analysis) and Western blotting. The activities of pertinent signaling pathways and expression of apoptosis-related proteins were measured by Western blotting.Results: Vertical blockade induced a more sustained inhibition of PI3K/Akt/mTOR signaling activities in all the HCC cells and HUVEC tested. Synergistic apoptosis-inducing effects, however, varied among different cell lines and drug combinations and were most prominent when NVP-AEW541 was combined with MK2206. Using an apoptosis array, we identified survivin as a potential downstream mediator. Over-expression of survivin in HCC cells abolished the anti-tumor synergy between NVP-AEW541 and MK2206, whereas knockdown of survivin improved the anti-tumor effects of all drug combinations tested. In vivo by xenograft studies confirmed the anti-tumor synergy between NVP-AEW541 and MK2206 and exhibited acceptable toxicity profiles.Conclusions: Vertical blockade of the IGFR/PI3K/Akt/mTOR pathway has promising anti-tumor activity for HCC. Survivin expression may serve as a biomarker to predict treatment efficacy. ? 2014 Ou et al.; licensee BioMed Central Ltd. | - |
dc.relation.ispartof | Molecular Cancer | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1,2,4 triazolo[3,4 f][1,6]naphthyridin 3(2h) one; dactolisib; everolimus; mammalian target of rapamycin; nvp aew 541; phosphatidylinositol 3 kinase; protein kinase B; somatomedin receptor; survivin; animal experiment; animal model; antineoplastic activity; apoptosis; article; cancer cell culture; controlled study; dose response; drug efficacy; drug potentiation; enzyme inhibition; flow cytometry; gene overexpression; gene silencing; human; human cell; in vitro study; liver cell carcinoma; male; mediator; molecularly targeted therapy; mouse; nonhuman; protein expression; tumor xenograft; umbilical vein endothelial cell; Western blotting; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Drug Synergism; Enzyme Inhibitors; Flow Cytometry; Heterocyclic Compounds, 3-Ring; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Liver Neoplasms; Male; Mice, Inbred BALB C; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Quinolines; Receptors, Somatomedin; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Tumor Markers, Biological; Xenograft Model Antitumor Assays | - |
dc.title | Vertical blockade of the IGFR- PI3K/Akt/mTOR pathway for the treatment of hepatocellular carcinoma: The role of survivin | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1186/1476-4598-13-2 | - |
dc.identifier.pmid | 24387108 | - |
dc.identifier.scopus | 2-s2.0-84891651341 | - |
dc.relation.pages | 2 | - |
dc.relation.journalvolume | 13 | - |
dc.relation.journalissue | 1 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Medical Oncology-NTUCC | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.orcid | 0000-0002-8368-1141 | - |
crisitem.author.orcid | 0000-0002-3561-1093 | - |
crisitem.author.orcid | 0000-0002-1122-0055 | - |
crisitem.author.orcid | 0000-0002-9152-6512 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學檢驗暨生物技術學系 |
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