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Conference Paper: Synergistic inhibitory effects of PTK787/ZK222584 and interferon-alfa on hepatocellular carcinoma with metastatic potential

TitleSynergistic inhibitory effects of PTK787/ZK222584 and interferon-alfa on hepatocellular carcinoma with metastatic potential
Authors
Issue Date2006
PublisherWiley-Blackwell Publishing Asia
Citation
Shanghai—Hong Kong International Liver Congress, Shanghai, China, 25–28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 n. S2, p. A94 How to Cite?
AbstractHepatocellular carcinoma (HCC) patients with metastatic diseasehave a dismal prognosis and effective therapy is urgently needed.Vas-cular endothelial growth factor (VEGF) plays an important role intumor angiogenesis and its receptor is highly expressed in HCC. Our previous study demonstrated that inhibition of VEGF receptors byPTK787/ZK222584 (PTK787) resulted in a significant reduction in tumor volumes in human HCC xenografts established by non-metastatic HCC cell lines. Interferon-alfa (IFN-α) is another agentwith an antiangiogenic property and administration of IFN-α at highdoses inhibited tumor growth in human HCC xenografts withmetastatic potential. The purpose of this study was to investigate theantitumor and antiangiogenic activities of PTK787 alone or in com-bination with IFN-α against HCC xenografts with metastatic poten-tial. The in vitro effect of PTK787 or/and IFN-α on proliferation ofmetastatic human HCC cell lines was studied by MTT assay, whereasapoptosis and cell cycle distribution were evaluated by flow cytome-try. Our results demonstrated that PTK787 inhibited tumor cell pro-liferation, induced tumor cells to undergo apoptosis and delayed cellcycle progression in vitro. IFN-α in combination with PTK787 inhib-ited endothelial cell, but not tumor cell, proliferation. PTK787administration significantly inhibited tumor growth and lung metas-tasis, whereas PTK787 in combination with IFN-α could result in afurther reduction of tumor growth and metastasis. This synergistictherapy significantly inhibited tumor microvessel density, VEGF andmatrix metalloproteinase-2 expression. Our data suggest that VEGFreceptor blockade in combination with IFN-α may provide an effec-tive therapeutic approach for human HCC.
Persistent Identifierhttp://hdl.handle.net/10722/108499
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.179

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorLi, Len_HK
dc.contributor.authorQian, Xen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorXu, Yen_HK
dc.contributor.authorSun, HCen_HK
dc.contributor.authorTang, ZYen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-26T00:42:12Z-
dc.date.available2010-09-26T00:42:12Z-
dc.date.issued2006en_HK
dc.identifier.citationShanghai—Hong Kong International Liver Congress, Shanghai, China, 25–28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 n. S2, p. A94en_HK
dc.identifier.issn0815-9319-
dc.identifier.urihttp://hdl.handle.net/10722/108499-
dc.description.abstractHepatocellular carcinoma (HCC) patients with metastatic diseasehave a dismal prognosis and effective therapy is urgently needed.Vas-cular endothelial growth factor (VEGF) plays an important role intumor angiogenesis and its receptor is highly expressed in HCC. Our previous study demonstrated that inhibition of VEGF receptors byPTK787/ZK222584 (PTK787) resulted in a significant reduction in tumor volumes in human HCC xenografts established by non-metastatic HCC cell lines. Interferon-alfa (IFN-α) is another agentwith an antiangiogenic property and administration of IFN-α at highdoses inhibited tumor growth in human HCC xenografts withmetastatic potential. The purpose of this study was to investigate theantitumor and antiangiogenic activities of PTK787 alone or in com-bination with IFN-α against HCC xenografts with metastatic poten-tial. The in vitro effect of PTK787 or/and IFN-α on proliferation ofmetastatic human HCC cell lines was studied by MTT assay, whereasapoptosis and cell cycle distribution were evaluated by flow cytome-try. Our results demonstrated that PTK787 inhibited tumor cell pro-liferation, induced tumor cells to undergo apoptosis and delayed cellcycle progression in vitro. IFN-α in combination with PTK787 inhib-ited endothelial cell, but not tumor cell, proliferation. PTK787administration significantly inhibited tumor growth and lung metas-tasis, whereas PTK787 in combination with IFN-α could result in afurther reduction of tumor growth and metastasis. This synergistictherapy significantly inhibited tumor microvessel density, VEGF andmatrix metalloproteinase-2 expression. Our data suggest that VEGFreceptor blockade in combination with IFN-α may provide an effec-tive therapeutic approach for human HCC.-
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Asia-
dc.relation.ispartofJournal of Gastroenterology and Hepatologyen_HK
dc.titleSynergistic inhibitory effects of PTK787/ZK222584 and interferon-alfa on hepatocellular carcinoma with metastatic potentialen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLiu, Y: ayliu@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailLi, L: lilei2968900@hotmail.comen_HK
dc.identifier.emailQian, X: sherrie@hkusua.hku.hken_HK
dc.identifier.emailChen, Y: cyc1sbs5@hkucc.hku.hken_HK
dc.identifier.emailXu, Y: xuyang@zshospital.neten_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1746.2006.04406.x-
dc.identifier.hkuros117109en_HK
dc.identifier.volume21en_HK
dc.identifier.issueSuppl 2en_HK
dc.identifier.spage94en_HK
dc.identifier.issnl0815-9319-

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