Cited 0 times in Scipus Cited Count

Inhibition of COX-2 in colon cancer modulates tumor growth and MDR-1 expression to enhance tumor regression in therapy-refractory cancers in vivo

DC Field Value Language
dc.contributor.authorRahman, M-
dc.contributor.authorSelvarajan, K-
dc.contributor.authorHasan, MR-
dc.contributor.authorChan, AP-
dc.contributor.authorJin, C-
dc.contributor.authorKim, J-
dc.contributor.authorChan, SK-
dc.contributor.authorLe, ND-
dc.contributor.authorKim, YB-
dc.contributor.authorTai, IT-
dc.date.accessioned2013-04-23T02:04:27Z-
dc.date.available2013-04-23T02:04:27Z-
dc.date.issued2012-
dc.identifier.issn1522-8002-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/7852-
dc.description.abstractHigher cyclooxygenase 2 (COX-2) expression is often observed in aggressive colorectal cancers (CRCs). Here, we attempt to examine the association between COX-2 expression in therapy-refractory CRC, how it affects chemosensitivity, and whether, in primary tumors, it is predictive of clinical outcomes. Our results revealed higher COX-2 expression in chemoresistant CRC cells and tumor xenografts. In vitro, the combination of either aspirin or celecoxib with 5-fluorouracil (5-FU) was capable of improving chemosensitivity in chemorefractory CRC cells, but a synergistic effect with 5-FU could only be demonstrated with celecoxib. To examine the potential clinical significance of these observations, in vivo studies were undertaken, which also showed that the greatest tumor regression was achieved in chemoresistant xenografts after chemotherapy in combination with celecoxib, but not aspirin. We also noted that these chemoresistant tumors with higher COX-2 expression had a more aggressive growth rate. Given the dramatic response to a combination of celecoxib + 5-FU, the possibility that celecoxib may modulate chemosensitivity as a result of its ability to inhibit MDR-1 was examined. In addition, assessment of a tissue microarray consisting of 130 cases of CRCs revealed that, in humans, higher COX-2 expression was associated with poorer survival with a 68% increased risk of mortality, indicating that COX-2 expression is a marker of poor clinical outcome. The findings of this study point to a potential benefit of combining COX-2 inhibitors with current regimens to achieve better response in the treatment of therapy-refractory CRC and in using COX-2 expression as a prognostic marker to help identify individuals who would benefit the greatest from closer follow-up and more aggressive therapy.-
dc.language.isoen-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents-
dc.subject.MESHApoptosis-
dc.subject.MESHAspirin-
dc.subject.MESHCell Cycle-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Proliferation-
dc.subject.MESHCell Survival-
dc.subject.MESHColonic Neoplasms-
dc.subject.MESHCyclooxygenase 2-
dc.subject.MESHCyclooxygenase 2 Inhibitors-
dc.subject.MESHDrug Resistance, Neoplasm-
dc.subject.MESHDrug Synergism-
dc.subject.MESHFemale-
dc.subject.MESHFluorouracil-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMiddle Aged-
dc.subject.MESHP-Glycoprotein-
dc.subject.MESHPyrazoles-
dc.subject.MESHSulfonamides-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleInhibition of COX-2 in colon cancer modulates tumor growth and MDR-1 expression to enhance tumor regression in therapy-refractory cancers in vivo-
dc.typeArticle-
dc.identifier.pmid22904679-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421958/-
dc.contributor.affiliatedAuthor김, 영배-
dc.type.localJournal Papers-
dc.citation.titleNeoplasia (New York, N.Y.)-
dc.citation.volume14-
dc.citation.number7-
dc.citation.date2012-
dc.citation.startPage624-
dc.citation.endPage633-
dc.identifier.bibliographicCitationNeoplasia (New York, N.Y.), 14(7). : 624-633, 2012-
dc.identifier.eissn1476-5586-
dc.relation.journalidJ015228002-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Files in This Item:
There are no files associated with this item.

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse