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Article: The potential role of hypoxia inducible factor 1α in tumor progression after hypoxia and chemotherapy in hepatocellular carcinoma

TitleThe potential role of hypoxia inducible factor 1α in tumor progression after hypoxia and chemotherapy in hepatocellular carcinoma
Authors
Issue Date2004
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2004, v. 64 n. 15, p. 5496-5503 How to Cite?
AbstractThis study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. Hypoxia was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. High-dose sodium salicylate was administered to achieve transcriptional blockade. Significant prolongation of animal survival was observed in the groups receiving hepatic artery ligation with cisplatin or sodium salicylate. Massive tumor cell necrosis and apoptosis were found in the ligation and all of the combined treatment groups. Up-regulation of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) at both mRNA and protein levels were detected in the groups receiving ligation and ligation with cisplatin, whereas a decreased level of von Hippel-Lindau tumor suppressor protein was identified in the group receiving ligation with cisplatin. Sodium salicylate enhanced expression of von Hippel-Lindau tumor suppressor protein but down-regulated HIF-1α and VEGF levels after ligation with or without cisplatin. An increased number of activated hepatic stellate cells in the tumors were observed in the ligation and ligation with cisplatin groups, whereas they were greatly reduced by sodium salicylate. In vitro study revealed that under hypoxic condition, both cisplatin and sodium salicylate could remarkably augment P53 and caspase 3 levels. Cisplatin stimulated HIF-1α up-regulation, whereas sodium salicylate suppressed HIF-1α expression. In conclusion, tumor progression after hypoxia and chemotherapy might be related to up-regulation of HIF-1α and subsequent VEGF production, and transcriptional blockade by sodium salicylate could enhance the therapeutic efficacy of hypoxia and chemotherapy.
Persistent Identifierhttp://hdl.handle.net/10722/172943
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, ZFen_US
dc.contributor.authorPoon, RTPen_US
dc.contributor.authorTo, Jen_US
dc.contributor.authorHo, DWen_US
dc.contributor.authorFan, STen_US
dc.date.accessioned2012-10-30T06:25:56Z-
dc.date.available2012-10-30T06:25:56Z-
dc.date.issued2004en_US
dc.identifier.citationCancer Research, 2004, v. 64 n. 15, p. 5496-5503en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://hdl.handle.net/10722/172943-
dc.description.abstractThis study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. Hypoxia was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. High-dose sodium salicylate was administered to achieve transcriptional blockade. Significant prolongation of animal survival was observed in the groups receiving hepatic artery ligation with cisplatin or sodium salicylate. Massive tumor cell necrosis and apoptosis were found in the ligation and all of the combined treatment groups. Up-regulation of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) at both mRNA and protein levels were detected in the groups receiving ligation and ligation with cisplatin, whereas a decreased level of von Hippel-Lindau tumor suppressor protein was identified in the group receiving ligation with cisplatin. Sodium salicylate enhanced expression of von Hippel-Lindau tumor suppressor protein but down-regulated HIF-1α and VEGF levels after ligation with or without cisplatin. An increased number of activated hepatic stellate cells in the tumors were observed in the ligation and ligation with cisplatin groups, whereas they were greatly reduced by sodium salicylate. In vitro study revealed that under hypoxic condition, both cisplatin and sodium salicylate could remarkably augment P53 and caspase 3 levels. Cisplatin stimulated HIF-1α up-regulation, whereas sodium salicylate suppressed HIF-1α expression. In conclusion, tumor progression after hypoxia and chemotherapy might be related to up-regulation of HIF-1α and subsequent VEGF production, and transcriptional blockade by sodium salicylate could enhance the therapeutic efficacy of hypoxia and chemotherapy.en_US
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_US
dc.relation.ispartofCancer Researchen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal - Pharmacologyen_US
dc.subject.meshAntineoplastic Agents - Therapeutic Useen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCarcinoma, Hepatocellular - Drug Therapy - Pathologyen_US
dc.subject.meshCaspase 3en_US
dc.subject.meshCaspases - Metabolismen_US
dc.subject.meshCell Hypoxiaen_US
dc.subject.meshCisplatin - Therapeutic Useen_US
dc.subject.meshCombined Modality Therapyen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshHsp90 Heat-Shock Proteins - Metabolismen_US
dc.subject.meshHepatic Arteryen_US
dc.subject.meshHypoxia-Inducible Factor 1, Alpha Subuniten_US
dc.subject.meshLiver - Metabolism - Pathologyen_US
dc.subject.meshLiver Neoplasms - Drug Therapy - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshNecrosisen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Bufen_US
dc.subject.meshSodium Salicylate - Pharmacologyen_US
dc.subject.meshSurvival Rateen_US
dc.subject.meshTranscription Factors - Genetics - Metabolismen_US
dc.subject.meshTumor Suppressor Protein P53 - Metabolismen_US
dc.subject.meshTumor Suppressor Proteins - Metabolismen_US
dc.subject.meshUbiquitin-Protein Ligases - Metabolismen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshVascular Endothelial Growth Factor A - Genetics - Metabolismen_US
dc.subject.meshVon Hippel-Lindau Tumor Suppressor Proteinen_US
dc.titleThe potential role of hypoxia inducible factor 1α in tumor progression after hypoxia and chemotherapy in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-03-3311en_US
dc.identifier.pmid15289360-
dc.identifier.scopuseid_2-s2.0-3442881606en_US
dc.identifier.hkuros93955-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3442881606&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume64en_US
dc.identifier.issue15en_US
dc.identifier.spage5496en_US
dc.identifier.epage5503en_US
dc.identifier.isiWOS:000223038200063-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYang, ZF=14018809600en_US
dc.identifier.scopusauthoridPoon, RTP=7103097223en_US
dc.identifier.scopusauthoridTo, J=36641520100en_US
dc.identifier.scopusauthoridHo, DW=7402971906en_US
dc.identifier.scopusauthoridFan, ST=7402678224en_US

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