NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells
DC Field | Value | Language |
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dc.contributor.author | Moon, Du G. | - |
dc.contributor.author | Lee, Sang E. | - |
dc.contributor.author | Oh, Mi M. | - |
dc.contributor.author | Lee, Sang C. | - |
dc.contributor.author | Jeong, Seong J. | - |
dc.contributor.author | Hong, Sung K. | - |
dc.contributor.author | Yoon, Cheol Y. | - |
dc.contributor.author | Byun, Seok S. | - |
dc.contributor.author | Park, Hong S. | - |
dc.contributor.author | Cheon, Jun | - |
dc.date.accessioned | 2021-09-05T05:49:46Z | - |
dc.date.available | 2021-09-05T05:49:46Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-09 | - |
dc.identifier.issn | 1019-6439 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/97582 | - |
dc.description.abstract | The PI3K/Akt/mTOR pathway is a prototypic survival pathway and constitutively activated in many malignant conditions. Moreover, activation of the PI3K/Akt/mTOR pathway confers resistance to various cancer therapies and is often associated with a poor prognosis. In this study, we explored the antitumor effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor in cisplatin-resistant human bladder cancer cells and its synergistic interaction with cisplatin. A human bladder cancer cell line with cisplatin resistance was exposed to escalating doses of NVP-BEZ235 alone or in combination with cisplatin and antitumor effects was determined by the CCK-8 assay. Based on a dose-response study, synergistic interaction between NVP-BEZ235 and cisplatin was evaluated by combination index (CI), three-dimensional model and clonogenic assay. The combination of NVP-BEZ235 and cisplatin caused significant synergistic antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range and reduced the IC50 of NVP-BEZ235 and cisplatin by 5.6- and 3.6-fold, respectively. Three-dimensional synergy analysis resulted in a synergy volume of 388.25 mu M/ml(2)% indicating a strong synergistic effect of combination therapy. The combination therapy caused cell cycle arrest and caspase-dependent apoptosis. Although NVP-BEZ235 suppressed PI3K/mTOR signaling without any paradoxical induction of Akt activity, it caused MEK/ERK pathway activation. The present study demonstrated that the PI3K/mTOR dual inhibitor NVP-BEZ235 can synergistically potentiate the antitumor effects of cisplatin in cisplatin-resistant bladder cancer cells though the suppression of cell cycle progression and the survival pathway as well as induction of caspase-dependent apoptosis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | SPANDIDOS PUBL LTD | - |
dc.subject | PHOSPHATIDYLINOSITOL-3 KINASE PATHWAY | - |
dc.subject | MTOR INHIBITOR | - |
dc.subject | OVARIAN-CANCER | - |
dc.subject | PI3K/AKT/MTOR PATHWAY | - |
dc.subject | UROTHELIAL CARCINOMA | - |
dc.subject | THERAPEUTIC STRATEGY | - |
dc.subject | MAMMALIAN TARGET | - |
dc.subject | URINARY-BLADDER | - |
dc.subject | IN-VITRO | - |
dc.subject | COMBINATION | - |
dc.title | NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Moon, Du G. | - |
dc.contributor.affiliatedAuthor | Oh, Mi M. | - |
dc.contributor.affiliatedAuthor | Park, Hong S. | - |
dc.contributor.affiliatedAuthor | Cheon, Jun | - |
dc.identifier.doi | 10.3892/ijo.2014.2505 | - |
dc.identifier.scopusid | 2-s2.0-84904397559 | - |
dc.identifier.wosid | 000339456000013 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF ONCOLOGY, v.45, no.3, pp.1027 - 1035 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF ONCOLOGY | - |
dc.citation.title | INTERNATIONAL JOURNAL OF ONCOLOGY | - |
dc.citation.volume | 45 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1027 | - |
dc.citation.endPage | 1035 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | PHOSPHATIDYLINOSITOL-3 KINASE PATHWAY | - |
dc.subject.keywordPlus | MTOR INHIBITOR | - |
dc.subject.keywordPlus | OVARIAN-CANCER | - |
dc.subject.keywordPlus | PI3K/AKT/MTOR PATHWAY | - |
dc.subject.keywordPlus | UROTHELIAL CARCINOMA | - |
dc.subject.keywordPlus | THERAPEUTIC STRATEGY | - |
dc.subject.keywordPlus | MAMMALIAN TARGET | - |
dc.subject.keywordPlus | URINARY-BLADDER | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | COMBINATION | - |
dc.subject.keywordAuthor | urinary bladder | - |
dc.subject.keywordAuthor | carcinoma | - |
dc.subject.keywordAuthor | resistance | - |
dc.subject.keywordAuthor | cisplatin | - |
dc.subject.keywordAuthor | NVP-BEZ235 | - |
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