File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Anti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma

TitleAnti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma
Authors
KeywordsHepatocellular carcinoma
Human recombinant arginase
Novel therapy
Preclinical study
Survivin
Issue Date2012
PublisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/ccdt/index.htm
Citation
Current Cancer Drug Targets, 2012, v. 12 n. 9, p. 1233-1243 How to Cite?
AbstractHepatocellular carcinoma (HCC) is considered as auxotrophic for arginine and BCT-100, a new recombinant human arginase, has been synthesized for arginine deprivation to inhibit arginine-dependent tumor growth. The aim of the present study was to evaluate the effects of BCT-100 on the inhibition of in vitro cell proliferation of HCC cell lines and in vivo tumor growth. The molecular mechanism involved was also studied. The anti-tumor efficacy of BCT-100 on cell proliferation, cell cycle distribution and cellular apoptosis were determined in human hepatoma HepG2 and PLC/PRF/5 cells. Protein expression in the Wnt/beta-catenin and Akt signaling pathways were analyzed by western blotting. Tumors were also established subcutaneously and BCT-100, in combination with oxaliplatin, was administrated i.p. to study the anti-tumor growth of the drugs. Treatment with BCT-100 was found to inhibit cell proliferation and enhance caspasedependent cellular apoptosis. Cell cycle arrest at S phase was observed. Inhibition of Wnt/beta-catenin and Akt signaling pathways, with a reduction in survivin and XIAP protein expressions, were also observed. Furthermore, combined treatment of BCT-100 and chemotherapy with oxaliplatin demonstrated synergistic inhibiting effect on tumor growth and the overall survival probability was enhanced as compared with BCT-100 or oxaliplatin treatment alone. These preclinical data demonstrate robust anti-tumor activity of BCT100 in HCC, thus providing the basis for its exploitation as a potential therapeutic agent in arginine-driven tumors. The positive effect of testing BCT100 with oxaliplatin in PLC/PRF/5 tumours also supports the rationale of combining BCT-100 and oxaliplatin in the clinical treatment of HCC.
Persistent Identifierhttp://hdl.handle.net/10722/164277
ISSN
2015 Impact Factor: 3.707
2015 SCImago Journal Rankings: 1.537

 

DC FieldValueLanguage
dc.contributor.authorChow, AKMen_US
dc.contributor.authorNg, Len_US
dc.contributor.authorLi, HSen_US
dc.contributor.authorCheng, CWen_US
dc.contributor.authorLam, CSCen_US
dc.contributor.authorYau, TCCen_US
dc.contributor.authorCheng, PNMen_US
dc.contributor.authorFan, STen_US
dc.contributor.authorPoon, RTPen_US
dc.contributor.authorPang, RWCen_US
dc.date.accessioned2012-09-20T07:57:33Z-
dc.date.available2012-09-20T07:57:33Z-
dc.date.issued2012en_US
dc.identifier.citationCurrent Cancer Drug Targets, 2012, v. 12 n. 9, p. 1233-1243en_US
dc.identifier.issn1568-0096-
dc.identifier.urihttp://hdl.handle.net/10722/164277-
dc.description.abstractHepatocellular carcinoma (HCC) is considered as auxotrophic for arginine and BCT-100, a new recombinant human arginase, has been synthesized for arginine deprivation to inhibit arginine-dependent tumor growth. The aim of the present study was to evaluate the effects of BCT-100 on the inhibition of in vitro cell proliferation of HCC cell lines and in vivo tumor growth. The molecular mechanism involved was also studied. The anti-tumor efficacy of BCT-100 on cell proliferation, cell cycle distribution and cellular apoptosis were determined in human hepatoma HepG2 and PLC/PRF/5 cells. Protein expression in the Wnt/beta-catenin and Akt signaling pathways were analyzed by western blotting. Tumors were also established subcutaneously and BCT-100, in combination with oxaliplatin, was administrated i.p. to study the anti-tumor growth of the drugs. Treatment with BCT-100 was found to inhibit cell proliferation and enhance caspasedependent cellular apoptosis. Cell cycle arrest at S phase was observed. Inhibition of Wnt/beta-catenin and Akt signaling pathways, with a reduction in survivin and XIAP protein expressions, were also observed. Furthermore, combined treatment of BCT-100 and chemotherapy with oxaliplatin demonstrated synergistic inhibiting effect on tumor growth and the overall survival probability was enhanced as compared with BCT-100 or oxaliplatin treatment alone. These preclinical data demonstrate robust anti-tumor activity of BCT100 in HCC, thus providing the basis for its exploitation as a potential therapeutic agent in arginine-driven tumors. The positive effect of testing BCT100 with oxaliplatin in PLC/PRF/5 tumours also supports the rationale of combining BCT-100 and oxaliplatin in the clinical treatment of HCC.-
dc.languageengen_US
dc.publisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/ccdt/index.htm-
dc.relation.ispartofCurrent Cancer Drug Targetsen_US
dc.subjectHepatocellular carcinoma-
dc.subjectHuman recombinant arginase-
dc.subjectNovel therapy-
dc.subjectPreclinical study-
dc.subjectSurvivin-
dc.titleAnti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailChow, AKM: chowakm@hku.hken_US
dc.identifier.emailNg, L: luing@hku.hken_US
dc.identifier.emailCheng, CW: timwai@hku.hken_US
dc.identifier.emailYau, TCC: tyaucc@hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.emailPang, RWC: robertap@hku.hken_US
dc.identifier.authorityYau, TCC=rp01466en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.authorityPang, RWC=rp00274en_US
dc.identifier.doi10.2174/15680096112091233-
dc.identifier.pmid22873218-
dc.identifier.scopuseid_2-s2.0-84872516259-
dc.identifier.hkuros206153en_US
dc.identifier.volume12en_US
dc.identifier.issue9-
dc.identifier.spage1233-
dc.identifier.epage1243-
dc.publisher.placeNetherlands-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats