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Conference Paper: Discruption of akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapy

TitleDiscruption of akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapy
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010. How to Cite?
AbstractPURPOSE: This study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. EXPERIMENTAL DESIGNS: Cell viability after cisplatin treatments under normoxia and hypoxia would be measured by 3,[4,5-dimethylthiazol-2-yl] -2,5-diphenyl-tetrazolium bromide (MTT) assay and cytofluorometric annexin-V apoptotic assay would be used to compare the apoptotic cells induced by cisplatin under normoxia and hypoxia. Western blotting would be employed to determine the akt/hif1 signaling. In vivo hypoxic condition was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. Hif1 inhibitor was administered to blockade Hif-1α expression both in vitro and in vivo. RESULTS: Cell viability was higher under hypoxic than normoxic conditions shown by MTT assay and decreased apoptotic cells could be observed by apoptotic assay under hypoxia. Hif-1α and akt were regulated each other under hypoxic conditions to confer cisplatin resistance in vitro. In an rat orthotopic hepatoma model, combining blockade of Hif-1α activity with ischemic hypoxia significantly enhanced the efficacy of chemotherapy, leading to suppression of tumor growth and prolongation of animal survival. CONCLUSION: Combined Hif1 inhibitor with hypoxia and chemotherapy can be a new and promising therapeutic approach to the treatment of HCC.
DescriptionPoster Session 21 - Combination Chemotherapy: abstract no. 5377
Persistent Identifierhttp://hdl.handle.net/10722/126973
ISSN

 

DC FieldValueLanguage
dc.contributor.authorLau, CKen_HK
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorHo, WYen_HK
dc.contributor.authorNg, Men_HK
dc.contributor.authorPoon, TPen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-10-31T12:59:06Z-
dc.date.available2010-10-31T12:59:06Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010.en_HK
dc.identifier.issn1948-3279-
dc.identifier.urihttp://hdl.handle.net/10722/126973-
dc.descriptionPoster Session 21 - Combination Chemotherapy: abstract no. 5377-
dc.description.abstractPURPOSE: This study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. EXPERIMENTAL DESIGNS: Cell viability after cisplatin treatments under normoxia and hypoxia would be measured by 3,[4,5-dimethylthiazol-2-yl] -2,5-diphenyl-tetrazolium bromide (MTT) assay and cytofluorometric annexin-V apoptotic assay would be used to compare the apoptotic cells induced by cisplatin under normoxia and hypoxia. Western blotting would be employed to determine the akt/hif1 signaling. In vivo hypoxic condition was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. Hif1 inhibitor was administered to blockade Hif-1α expression both in vitro and in vivo. RESULTS: Cell viability was higher under hypoxic than normoxic conditions shown by MTT assay and decreased apoptotic cells could be observed by apoptotic assay under hypoxia. Hif-1α and akt were regulated each other under hypoxic conditions to confer cisplatin resistance in vitro. In an rat orthotopic hepatoma model, combining blockade of Hif-1α activity with ischemic hypoxia significantly enhanced the efficacy of chemotherapy, leading to suppression of tumor growth and prolongation of animal survival. CONCLUSION: Combined Hif1 inhibitor with hypoxia and chemotherapy can be a new and promising therapeutic approach to the treatment of HCC.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Research-
dc.titleDiscruption of akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapyen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLau, CK: lauck@hku.hken_HK
dc.identifier.emailYang, ZF: zfyang@hku.hken_HK
dc.identifier.emailHo, WY: davidho@HKUCC.hku.hken_HK
dc.identifier.emailNg, M: michaelnpng@gmail.comen_HK
dc.identifier.emailPoon, TP: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, TP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros175522en_HK
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010.-

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