Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/86466
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dc.contributor.authorTsai, Hsiao-Chizh_TW
dc.contributor.authorHuang, Chun-Yinzh_TW
dc.contributor.authorSu, Hong-Linzh_TW
dc.contributor.authorTang, Chih-Hsinzh_TW
dc.date2014-
dc.date.accessioned2015-08-04T05:58:15Z-
dc.date.available2015-08-04T05:58:15Z-
dc.identifier.issn1932-6203zh_TW
dc.identifier.issn1932-6203zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/86466-
dc.description.abstractOsteosarcoma (OS) is the most common form of malignant bone tumor and is an aggressive malignant neoplasm exhibiting osteoblastic differentiation. Cisplatin is one of the most efficacious antitumor drugs for osteosarcoma patients. However, treatment failures are common due to the development of chemoresistance. CCN2 (also known as CTGF), is a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CCN2 in cisplatin-mediated chemotherapy is still unknown. Here, we found that CCN2 was upregulated in human osteosarcoma cells after treatment with cisplatin. Moreover, overexpression of CCN2 increased the resistance to cisplatin-mediated cell apoptosis. In contrast, reduction of CCN2 by CCN2 shRNA promoted the chemotherapeutic effect of cisplatin. We also found that CCN2 provided resistance to cisplatin-induced apoptosis through upregulation of Bcl-xL and survivin. Knockdown of Bcl-xL or survivin removed the CCN2-mediated resistance to apoptosis induced by cisplatin. On the other hand, CCN2 also promoted FAK, MEK, and ERK survival signaling pathways to enhance tumor survival during cisplatin treatment. In a mouse xenograft model, overexpression of CCN2 promoted resistance to cisplatin. However, knockdown of CCN2 increased the therapeutic effect of cisplatin. Therefore, our data suggest that CCN2 might be a critical oncogene of human osteosarcoma for cisplatin-resistance and supported osteosarcoma cell growth in vivo and in vitro.zh_TW
dc.language.isoenzh_TW
dc.relationPLoS ONE, Volume 9, Issue 3, Page(s) e90159.zh_TW
dc.subjectAnimalszh_TW
dc.subjectAntineoplastic Agentszh_TW
dc.subjectApoptosiszh_TW
dc.subjectBone Neoplasmszh_TW
dc.subjectCell Deathzh_TW
dc.subjectCell Line, Tumorzh_TW
dc.subjectCisplatinzh_TW
dc.subjectConnective Tissue Growth Factorzh_TW
dc.subjectDisease Models, Animalzh_TW
dc.subjectDrug Resistance, Neoplasmzh_TW
dc.subjectFocal Adhesion Protein-Tyrosine Kinaseszh_TW
dc.subjectGene Expression Regulation, Neoplasticzh_TW
dc.subjectHumanszh_TW
dc.subjectInhibitor of Apoptosis Proteinszh_TW
dc.subjectMAP Kinase Signaling Systemzh_TW
dc.subjectOsteosarcomazh_TW
dc.subjectTumor Burdenzh_TW
dc.subjectXenograft Model Antitumor Assayszh_TW
dc.subjectbcl-X Proteinzh_TW
dc.titleCCN2 Enhances Resistance to Cisplatin-Mediating Cell Apoptosis in Human Osteosarcomazh_TW
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1371/journal.pone.0090159zh_TW
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.cerifentitytypePublications-
item.fulltextwith fulltext-
item.languageiso639-1en-
item.grantfulltextrestricted-
Appears in Collections:生命科學系所
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