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Article: Both antiangiogenesis- and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584

TitleBoth antiangiogenesis- and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2005, v. 65 n. 9, p. 3691-3699 How to Cite?
AbstractVascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis of hepatocellular carcinoma. Inhibition of VEGF receptors could theoretically reduce angiogenesis and tumor growth in hepatocellular carcinoma, but this remains to be proven with an experimental study. This study examined the angiogenesis-dependent and angiogenesis-independent activities of PTK787/ZK222584 (PTK787), a tyrosine kinase inhibitor of VEGF receptors, in nude mice bearing human hepatocellular carcinoma xenografts. The in vitro effects of PTK787 on proliferation, apoptosis, and cell cycle distribution in human hepatocellular carcinoma cell lines were also studied. Oral administration of PTK787 resulted in a significant reduction in tumor volume and microvessel formation of hepatocellular carcinoma xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis both in vivo and in vitro. The proapoptotic response was associated with down-regulation of Bcl-2 and Bcl-x L expression and induction of cleavage of caspase-3. In addition, PTK787 induced growth arrest in hepatocellular carcinoma cells, which was associated with G 1 arrest and partial G 2-M block. This effect correlated with an increase in p21 WAF1/CIP1 (p21) and p27 KIP1 (p27) protein expression. In conclusion, this study showed that PTK787 is a potent inhibitor of tumor growth in hepatocellular carcinoma by both antiangiogenic effect and direct effects on tumor cell proliferation and apoptosis. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human hepatocellular carcinoma. ©2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/83928
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorLi, Qen_HK
dc.contributor.authorKok, TWen_HK
dc.contributor.authorLau, Cen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:46:53Z-
dc.date.available2010-09-06T08:46:53Z-
dc.date.issued2005en_HK
dc.identifier.citationCancer Research, 2005, v. 65 n. 9, p. 3691-3699en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83928-
dc.description.abstractVascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis of hepatocellular carcinoma. Inhibition of VEGF receptors could theoretically reduce angiogenesis and tumor growth in hepatocellular carcinoma, but this remains to be proven with an experimental study. This study examined the angiogenesis-dependent and angiogenesis-independent activities of PTK787/ZK222584 (PTK787), a tyrosine kinase inhibitor of VEGF receptors, in nude mice bearing human hepatocellular carcinoma xenografts. The in vitro effects of PTK787 on proliferation, apoptosis, and cell cycle distribution in human hepatocellular carcinoma cell lines were also studied. Oral administration of PTK787 resulted in a significant reduction in tumor volume and microvessel formation of hepatocellular carcinoma xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis both in vivo and in vitro. The proapoptotic response was associated with down-regulation of Bcl-2 and Bcl-x L expression and induction of cleavage of caspase-3. In addition, PTK787 induced growth arrest in hepatocellular carcinoma cells, which was associated with G 1 arrest and partial G 2-M block. This effect correlated with an increase in p21 WAF1/CIP1 (p21) and p27 KIP1 (p27) protein expression. In conclusion, this study showed that PTK787 is a potent inhibitor of tumor growth in hepatocellular carcinoma by both antiangiogenic effect and direct effects on tumor cell proliferation and apoptosis. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human hepatocellular carcinoma. ©2005 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.titleBoth antiangiogenesis- and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=65&issue=9&spage=3691&epage=3699&date=2005&atitle=Both+antiangiogenesis-+and+angiogenesis-independent+effects+are+responsible+for+hepatocellular+carcinoma+growth+arrest+by+tyrosine+kinase+inhibitor+PTK787/ZK222584en_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-04-3462en_HK
dc.identifier.pmid15867364-
dc.identifier.scopuseid_2-s2.0-18144401256en_HK
dc.identifier.hkuros97898en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-18144401256&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue9en_HK
dc.identifier.spage3691en_HK
dc.identifier.epage3699en_HK
dc.identifier.isiWOS:000228656000028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, Y=14627533300en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridLi, Q=8639537800en_HK
dc.identifier.scopusauthoridKok, TW=36851058500en_HK
dc.identifier.scopusauthoridLau, C=8086563300en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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