Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug resistance protein 4 (MRP4) via PGE(2)-dependent pathway
DC Field | Value | Language |
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dc.contributor.author | Maeng, Han-Joo | - |
dc.contributor.author | Lee, Wook-Joo | - |
dc.contributor.author | Jin, Qing-Ri | - |
dc.contributor.author | Chang, Ji-Eun | - |
dc.contributor.author | Shim, Won-Sik | - |
dc.date.available | 2020-02-28T15:46:31Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2014-10 | - |
dc.identifier.issn | 0928-0987 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12211 | - |
dc.description.abstract | It is apparent that lung cancer is associated with inflammation, with accompanying hallmark elevations of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE(2)) levels. However, the effects of these changes on MRP efflux transporters have not been thoroughly investigated before. Here, we report that upregulation of COX-2 can induce overexpression of MRP4 in both A549 non-small-cell lung cancer cell lines and mouse lung cancer models. In A549 cells, phorbol 12-myristate 13-acetate (PMA) treatment induced upregulation of COX-2 and MRP4 together, but not other MRP transporters. Transient overexpression of human COX-2 cDNA also specifically increased COX-2 and MRP4. Moreover, COX inhibitor treatment and COX-2-specific siRNA significantly inhibited the upregulation of MRP4. Additionally, PMA-treatment increased extracellular PGE(2) levels, likely due to increased MRP4 function. Likewise, COX-2-specific siRNA reduced extracellular PGE(2) levels. Furthermore, COX-2 upregulation resulted in an increase in mPGES-1, an enzyme responsible for PGE(2) production. Finally, metastasized lung cancer model mice exhibited increased expression levels of COX-2 and MRP4, as well as mPGES-1. In conclusion, the present study suggests that overexpression of MRP4 in lung cancer may be attributable to COX-2 upregulation via a PGE(2)-dependent pathway. (C) 2014 Elsevier B.V. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.relation.isPartOf | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | - |
dc.title | Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug resistance protein 4 (MRP4) via PGE(2)-dependent pathway | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000340301500023 | - |
dc.identifier.doi | 10.1016/j.ejps.2014.05.023 | - |
dc.identifier.bibliographicCitation | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.62, pp.189 - 196 | - |
dc.identifier.scopusid | 2-s2.0-84903267487 | - |
dc.citation.endPage | 196 | - |
dc.citation.startPage | 189 | - |
dc.citation.title | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | - |
dc.citation.volume | 62 | - |
dc.contributor.affiliatedAuthor | Maeng, Han-Joo | - |
dc.contributor.affiliatedAuthor | Lee, Wook-Joo | - |
dc.contributor.affiliatedAuthor | Shim, Won-Sik | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Multidrug resistance associated protein 4 (MRP4) | - |
dc.subject.keywordAuthor | Cyclooxygenase 2 (COX-2) | - |
dc.subject.keywordAuthor | Prostaglandin E2 (PGE(2)) | - |
dc.subject.keywordAuthor | Lung cancer | - |
dc.subject.keywordPlus | CONFERS RESISTANCE | - |
dc.subject.keywordPlus | CYCLOOXYGENASE-2 EXPRESSION | - |
dc.subject.keywordPlus | TARGETING CYCLOOXYGENASE-2 | - |
dc.subject.keywordPlus | EFFLUX TRANSPORTER | - |
dc.subject.keywordPlus | HUMAN PULMONARY | - |
dc.subject.keywordPlus | DRUG RESPONSE | - |
dc.subject.keywordPlus | KAPPA-B | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MRP4/ABCC4 | - |
dc.subject.keywordPlus | GROWTH | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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