Please use this identifier to cite or link to this item: https://doi.org/10.1158/1535-7163.MCT-07-0162
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dc.titleAZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma
dc.contributor.authorHuynh, H
dc.contributor.authorChow, P.K.H
dc.contributor.authorSoo, K.-C
dc.date.accessioned2020-10-20T04:46:07Z
dc.date.available2020-10-20T04:46:07Z
dc.date.issued2007
dc.identifier.citationHuynh, H, Chow, P.K.H, Soo, K.-C (2007). AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma. Molecular Cancer Therapeutics 6 (9) : 2468-2476. ScholarBank@NUS Repository. https://doi.org/10.1158/1535-7163.MCT-07-0162
dc.identifier.issn15357163
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/177992
dc.description.abstractHepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with no effective treatment for most individuals who succumb to this neoplasm. We report that treatment of primary HCC cells with the mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase 1/2 inhibitor AZD6244 (ARRY-142886) plus doxorubicin led to synergistic growth inhibition and apoptosis. In vivo administration of AZD6244, doxorubicin, or the combination of AZD6244 and doxorubicin in mice bearing 5-1318 HCC xenografts resulted in approximately 52% ± 15%, 12% ± 9%, and 76% ± 7% growth inhibition, respectively. AZD6244-inhibited tumor growth was associated with increased apoptosis, inactivation of ERK1/2, inhibition of cell proliferation, and down-regulation of cell cycle regulators, including cyclin D1, cdc-2, cyclin-dependent kinases 2 and 4, cyclin B1, and c-Myc. The AZD6244-doxorubicin combined protocol not only promoted apoptosis but also induced a synergistic effect not seen in single-agent-treated tumors, including increased expression of the p130 RB tumor suppressor gene. Our study provides a strong rationale for clinical investigation of combination therapy with the mitogen-activated protein/ERK kinase 1/2 inhibitor AZD6244 and doxorubicin in patients with HCC. Copyright © 2007 American Association for Cancer Research.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectazd 6244
dc.subjectcell cycle protein
dc.subjectcell cycle protein 2
dc.subjectcyclin B1
dc.subjectcyclin D1
dc.subjectcyclin dependent kinase 2
dc.subjectcyclin dependent kinase 4
dc.subjectdoxorubicin
dc.subjectmitogen activated protein kinase inhibitor
dc.subjectMyc protein
dc.subjectunclassified drug
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcancer cell culture
dc.subjectcancer combination chemotherapy
dc.subjectcancer growth
dc.subjectcancer inhibition
dc.subjectcell cycle
dc.subjectcell proliferation
dc.subjectclinical study
dc.subjectcombination chemotherapy
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectdrug potentiation
dc.subjectgene inactivation
dc.subjectliver cell carcinoma
dc.subjectmale
dc.subjectmouse
dc.subjectnonhuman
dc.subjectoncogene c myc
dc.subjectpriority journal
dc.subjecttumor xenograft
dc.subjectAnimals
dc.subjectAntibiotics, Antineoplastic
dc.subjectApoptosis
dc.subjectBenzimidazoles
dc.subjectBlotting, Western
dc.subjectCarcinoma, Hepatocellular
dc.subjectCell Cycle
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectCrk-Associated Substrate Protein
dc.subjectCyclins
dc.subjectDoxorubicin
dc.subjectDrug Therapy, Combination
dc.subjectFluorescent Antibody Technique
dc.subjectHumans
dc.subjectIn Situ Nick-End Labeling
dc.subjectLiver Neoplasms
dc.subjectMale
dc.subjectMice
dc.subjectMice, SCID
dc.subjectSurvival Rate
dc.subjectTransplantation, Heterologous
dc.typeArticle
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1158/1535-7163.MCT-07-0162
dc.description.sourcetitleMolecular Cancer Therapeutics
dc.description.volume6
dc.description.issue9
dc.description.page2468-2476
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