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Conference Paper: Blockage of vascular endothelial growth factor receptors by tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth of hepatocellular carcinoma with metastatic potential by angiogenesis-independent effect

TitleBlockage of vascular endothelial growth factor receptors by tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth of hepatocellular carcinoma with metastatic potential by angiogenesis-independent effect
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacr.org/home/scientists/meetings--workshops.aspx
Citation
AACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 474-475 Abstract no. 2027 How to Cite?
AbstractHepatocellular Carcinoma (HCC) is one of the most common malignancies and is responsible for more than one million deaths worldwide. Vascular endothelial growth factor (VEGF) receptors with tyrosine kinase activity are highly expressed in many human tumors. Therefore, inhibition of VEGF receptors could be a potential target for anticancer therapy. PTK787/ZK222584 (PTK787) is a potent tyrosine kinase inhibitor. In the previous studies, the antitumor activity of PTK787 was attributed to the inhibition of VEGF signaling in the tumor vasculature, and a direct antitumor effect on solid tumor was not reported. In this study, we investigated the direct effect of PTK787 in nude mice bearing human HCC xenograft with metastatic potential. Tumor tissues from a metastatic HCC nude mice model established by metastatic human HCC cell lines were implanted orthotopically in the liver of nude mice. The effect of PTK787 on proliferation of metastatic human HCC cell lines was studied by MTT assay. The in vitro effect of PTK787 on metastatic HCC cell line apoptosis and cell cycle distribution were evaluated by flow cytometry. Our results demonstrated that PTK787 oral administration to mice at 50 mg/kg/day resulted in a significant reduction in tumor growth of HCC xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis in vitro. Furthermore, PTK787 treatment induced a delay in cell cycle progression and a G1 arrest together with a partial G2/M block. In conclusion, this study demonstrated that PTK787 is a potent inhibitor of tumor growth in HCC with metastatic potential. The inhibition of tumor volume by PTK787 may through direct effects on inhibition of tumor cell proliferation, induction of tumor cell apoptosis and blocking tumor cell cycle progression. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human HCC.
Persistent Identifierhttp://hdl.handle.net/10722/107856
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-26T00:15:17Z-
dc.date.available2010-09-26T00:15:17Z-
dc.date.issued2005en_HK
dc.identifier.citationAACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 474-475 Abstract no. 2027-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/107856-
dc.description.abstractHepatocellular Carcinoma (HCC) is one of the most common malignancies and is responsible for more than one million deaths worldwide. Vascular endothelial growth factor (VEGF) receptors with tyrosine kinase activity are highly expressed in many human tumors. Therefore, inhibition of VEGF receptors could be a potential target for anticancer therapy. PTK787/ZK222584 (PTK787) is a potent tyrosine kinase inhibitor. In the previous studies, the antitumor activity of PTK787 was attributed to the inhibition of VEGF signaling in the tumor vasculature, and a direct antitumor effect on solid tumor was not reported. In this study, we investigated the direct effect of PTK787 in nude mice bearing human HCC xenograft with metastatic potential. Tumor tissues from a metastatic HCC nude mice model established by metastatic human HCC cell lines were implanted orthotopically in the liver of nude mice. The effect of PTK787 on proliferation of metastatic human HCC cell lines was studied by MTT assay. The in vitro effect of PTK787 on metastatic HCC cell line apoptosis and cell cycle distribution were evaluated by flow cytometry. Our results demonstrated that PTK787 oral administration to mice at 50 mg/kg/day resulted in a significant reduction in tumor growth of HCC xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis in vitro. Furthermore, PTK787 treatment induced a delay in cell cycle progression and a G1 arrest together with a partial G2/M block. In conclusion, this study demonstrated that PTK787 is a potent inhibitor of tumor growth in HCC with metastatic potential. The inhibition of tumor volume by PTK787 may through direct effects on inhibition of tumor cell proliferation, induction of tumor cell apoptosis and blocking tumor cell cycle progression. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human HCC.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacr.org/home/scientists/meetings--workshops.aspx-
dc.relation.ispartofCancer Researchen_HK
dc.titleBlockage of vascular endothelial growth factor receptors by tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth of hepatocellular carcinoma with metastatic potential by angiogenesis-independent effecten_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.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.hkuros99691en_HK
dc.identifier.hkuros119016-

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