TDP1 and TOP1 modulation in Olaparib-resistant cancer determines the efficacy of subsequent chemotherapy
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim J.W. | - |
dc.contributor.author | Min A. | - |
dc.contributor.author | Im S.-A. | - |
dc.contributor.author | Jang H. | - |
dc.contributor.author | Kim Y.J. | - |
dc.contributor.author | Kim H.-J. | - |
dc.contributor.author | Lee K.-H. | - |
dc.contributor.author | Kim T.-Y. | - |
dc.contributor.author | Lee K.W. | - |
dc.contributor.author | Oh D.-Y. | - |
dc.contributor.author | Kim J.-H. | - |
dc.contributor.author | Bang Y.-J. | - |
dc.date.available | 2020-04-16T08:21:20Z | - |
dc.date.issued | 2020-02 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/38530 | - |
dc.description.abstract | The aim of this study was to elucidate the carryover effect of olaparib to subsequent chemotherapy and its underlying mechanisms. We generated olaparib-resistant SNU-484, SNU-601, SNU-668, and KATO-III gastric cancer cell lines and confirmed their resistance by cell viability and colony forming assays. Notably, olaparib-resistant cell lines displayed cross-resistance to cisplatin except for KATO-III. Inversely, olaparib-resistant SNU-484, SNU-668, and KATO-III were more sensitive to irinotecan than their parental cells. However, sensitivity to paclitaxel remained unaltered. There were compensatory changes in the ATM/ATR axis and p-Chk1/2 protein expression. ERCC1 was also induced in olaparib-resistant SNU-484, SNU-601, and SNU-668, which showed cross-resistance to cisplatin. Olaparib-resistant cells showed tyrosyl-DNA phosphodiesterase 1 (TDP1) downregulation with higher topoisomerase 1 (TOP1) activity, which is a target of irinotecan. These changes of TOP1 and TDP1 in olaparib-resistant cells was confirmed as the underlying mechanism for increased irinotecan sensitivity through manipulated gene expression of TOP1 and TDP1 by specific plasmid transfection and siRNA. The patient-derived xenograft model established from the patient who acquired resistance to olaparib with BRCA2 mutation showed increased sensitivity in irinotecan. In conclusion, the carryover effects of olaparib to improve antitumor effect of subsequent irinotecan were demonstrated. These effects should be considered when determining the subsequent therapy with olaparib. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | MDPI AG | - |
dc.title | TDP1 and TOP1 modulation in Olaparib-resistant cancer determines the efficacy of subsequent chemotherapy | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/cancers12020334 | - |
dc.identifier.bibliographicCitation | Cancers, v.12, no.2 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000522477300080 | - |
dc.identifier.scopusid | 2-s2.0-85079231412 | - |
dc.citation.number | 2 | - |
dc.citation.title | Cancers | - |
dc.citation.volume | 12 | - |
dc.type.docType | Article | - |
dc.publisher.location | 스위스 | - |
dc.subject.keywordAuthor | Carryover effect | - |
dc.subject.keywordAuthor | Irinotecan | - |
dc.subject.keywordAuthor | Olaparib | - |
dc.subject.keywordAuthor | TDP1 | - |
dc.subject.keywordAuthor | TOP1 activity | - |
dc.subject.keywordPlus | ATM protein | - |
dc.subject.keywordPlus | ATR protein | - |
dc.subject.keywordPlus | checkpoint kinase 1 | - |
dc.subject.keywordPlus | checkpoint kinase 2 | - |
dc.subject.keywordPlus | cisplatin | - |
dc.subject.keywordPlus | excision repair cross complementing protein 1 | - |
dc.subject.keywordPlus | irinotecan | - |
dc.subject.keywordPlus | olaparib | - |
dc.subject.keywordPlus | oncoprotein | - |
dc.subject.keywordPlus | paclitaxel | - |
dc.subject.keywordPlus | small interfering RNA | - |
dc.subject.keywordPlus | topoisomerase 1 | - |
dc.subject.keywordPlus | tyrosyl DNA phosphodiesterase 1 | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | animal model | - |
dc.subject.keywordPlus | antineoplastic activity | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | bioassay | - |
dc.subject.keywordPlus | breast cancer | - |
dc.subject.keywordPlus | cancer morphology | - |
dc.subject.keywordPlus | cancer resistance | - |
dc.subject.keywordPlus | cell viability assay | - |
dc.subject.keywordPlus | colony forming assay | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | cross resistance | - |
dc.subject.keywordPlus | DNA damage response | - |
dc.subject.keywordPlus | down regulation | - |
dc.subject.keywordPlus | drug efficacy | - |
dc.subject.keywordPlus | drug targeting | - |
dc.subject.keywordPlus | enzyme activity | - |
dc.subject.keywordPlus | enzyme regulation | - |
dc.subject.keywordPlus | gene expression | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | human tissue | - |
dc.subject.keywordPlus | KATO III cell line | - |
dc.subject.keywordPlus | mouse | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | protein expression | - |
dc.subject.keywordPlus | SNU-484 cell line | - |
dc.subject.keywordPlus | SNU-601 cell line | - |
dc.subject.keywordPlus | SNU-668 cell line | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.