File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Effect of peroxisome proliferator activated receptor γ ligands on growth and gene expression profiles of gastric cancer cells

TitleEffect of peroxisome proliferator activated receptor γ ligands on growth and gene expression profiles of gastric cancer cells
Authors
Issue Date2004
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2004, v. 53 n. 3, p. 331-338 How to Cite?
AbstractBackground and aims: Although peroxisome proliferator activated receptor γ (PPARγ) agonists have been implicated in differentiation and growth inhibition of cancer cells, the potential therapeutic and chemopreventive effects on gastric cancer are poorly defined. We examined the in vitro and in vivo effects of PPARγ ligands on growth of gastric cancer, and the effect of PPARγ activation on expression of cyclooxygenase 2 (COX-2) and cancer related genes. Methods: Gastric cell lines (MKN28 and MKN45) were treated with two specific PPARγ ligands: ciglitazone and 15-deoxy-Δ 12,14-prostaglandin J 2. Cell growth was determined by bromodeoxyuridine incorporation assay and apoptosis was measured by DNA fragmentation. Expression of COX-2 was determined by western blot and real time quantitative polymerase chain reaction (PCR). Expression profiles of cancer related genes were screened with cDNA array. In vivo growth of implanted MKN45 cells in nude mice was monitored after oral treatment with rosiglitazone. Results: PPARγ ligands suppressed the in vitro growth of MKN45 cells in a dose dependent manner whereas prostacyclin, a PPARδ agonist, had no growth inhibitory effect. Growth inhibition was more pronounced in MKN45 cells, which was accompanied by DNA fragmentation and downregulation of COX-2. Screening by cDNA microarray showed that PPARγ ligand treatment was associated with upregulation of bad and p53, and downregulation of bcl-2, bcl-xl, and cyclin E1 in MKN45 cells, which was confirmed by quantitative real time PCR. In contrast, MKN28 cells with lower PPARγ and COX-2 expression levels had lower growth inhibitory responses to PPARγ ligands. Microarray experiments only showed induction of the bad gene in MKN28 cells. In vivo growth of MKN45 cells in nude mice was retarded by rosiglitazone. Mean tumour volume in rosiglitazone treated mice was significantly lower than controls at six weeks (p = 0.019) and seven weeks (p = 0.001) after treatment. Conclusions: PPARγ ligands suppress both in vitro and in vivo growth of gastric cancer and may play a major role in cancer therapy and prevention.
Persistent Identifierhttp://hdl.handle.net/10722/162769
ISSN
2015 Impact Factor: 14.921
2015 SCImago Journal Rankings: 6.474
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, WKen_US
dc.contributor.authorBai, Aen_US
dc.contributor.authorChan, VYWen_US
dc.contributor.authorYu, Jen_US
dc.contributor.authorChan, MWYen_US
dc.contributor.authorTo, KFen_US
dc.contributor.authorWu, JRen_US
dc.contributor.authorChan, KKen_US
dc.contributor.authorFu, YGen_US
dc.contributor.authorChan, FKLen_US
dc.contributor.authorSung, JJYen_US
dc.date.accessioned2012-09-05T05:23:17Z-
dc.date.available2012-09-05T05:23:17Z-
dc.date.issued2004en_US
dc.identifier.citationGut, 2004, v. 53 n. 3, p. 331-338en_US
dc.identifier.issn0017-5749en_US
dc.identifier.urihttp://hdl.handle.net/10722/162769-
dc.description.abstractBackground and aims: Although peroxisome proliferator activated receptor γ (PPARγ) agonists have been implicated in differentiation and growth inhibition of cancer cells, the potential therapeutic and chemopreventive effects on gastric cancer are poorly defined. We examined the in vitro and in vivo effects of PPARγ ligands on growth of gastric cancer, and the effect of PPARγ activation on expression of cyclooxygenase 2 (COX-2) and cancer related genes. Methods: Gastric cell lines (MKN28 and MKN45) were treated with two specific PPARγ ligands: ciglitazone and 15-deoxy-Δ 12,14-prostaglandin J 2. Cell growth was determined by bromodeoxyuridine incorporation assay and apoptosis was measured by DNA fragmentation. Expression of COX-2 was determined by western blot and real time quantitative polymerase chain reaction (PCR). Expression profiles of cancer related genes were screened with cDNA array. In vivo growth of implanted MKN45 cells in nude mice was monitored after oral treatment with rosiglitazone. Results: PPARγ ligands suppressed the in vitro growth of MKN45 cells in a dose dependent manner whereas prostacyclin, a PPARδ agonist, had no growth inhibitory effect. Growth inhibition was more pronounced in MKN45 cells, which was accompanied by DNA fragmentation and downregulation of COX-2. Screening by cDNA microarray showed that PPARγ ligand treatment was associated with upregulation of bad and p53, and downregulation of bcl-2, bcl-xl, and cyclin E1 in MKN45 cells, which was confirmed by quantitative real time PCR. In contrast, MKN28 cells with lower PPARγ and COX-2 expression levels had lower growth inhibitory responses to PPARγ ligands. Microarray experiments only showed induction of the bad gene in MKN28 cells. In vivo growth of MKN45 cells in nude mice was retarded by rosiglitazone. Mean tumour volume in rosiglitazone treated mice was significantly lower than controls at six weeks (p = 0.019) and seven weeks (p = 0.001) after treatment. Conclusions: PPARγ ligands suppress both in vitro and in vivo growth of gastric cancer and may play a major role in cancer therapy and prevention.en_US
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_US
dc.relation.ispartofGuten_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Agents - Therapeutic Useen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshCyclooxygenase 2en_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGene Expression Regulation, Neoplastic - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshIntracellular Signaling Peptides And Proteinsen_US
dc.subject.meshIsoenzymes - Metabolismen_US
dc.subject.meshLigandsen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Proteinsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshNeoplasm Proteins - Physiologyen_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshNuclear Receptor Coactivatorsen_US
dc.subject.meshProstaglandin D2 - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshProstaglandin-Endoperoxide Synthases - Metabolismen_US
dc.subject.meshStomach Neoplasms - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshThiazolidinediones - Pharmacology - Therapeutic Useen_US
dc.subject.meshTranscription Factors - Agonists - Physiologyen_US
dc.subject.meshTumor Cells, Cultured - Drug Effectsen_US
dc.titleEffect of peroxisome proliferator activated receptor γ ligands on growth and gene expression profiles of gastric cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailLeung, WK:waikleung@hku.hken_US
dc.identifier.authorityLeung, WK=rp01479en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1136/gut.2003.021105en_US
dc.identifier.pmid14960510-
dc.identifier.scopuseid_2-s2.0-10744231241en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-10744231241&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume53en_US
dc.identifier.issue3en_US
dc.identifier.spage331en_US
dc.identifier.epage338en_US
dc.identifier.isiWOS:000188896300005-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLeung, WK=7201504523en_US
dc.identifier.scopusauthoridBai, A=36952371700en_US
dc.identifier.scopusauthoridChan, VYW=8599737600en_US
dc.identifier.scopusauthoridYu, J=35351306800en_US
dc.identifier.scopusauthoridChan, MWY=7402597788en_US
dc.identifier.scopusauthoridTo, KF=7101911940en_US
dc.identifier.scopusauthoridWu, JR=7409258940en_US
dc.identifier.scopusauthoridChan, KK=8599737700en_US
dc.identifier.scopusauthoridFu, YG=8599738000en_US
dc.identifier.scopusauthoridChan, FKL=7202586434en_US
dc.identifier.scopusauthoridSung, JJY=36847007300en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats