Transport-mediated Oxaliplatin Resistance Associated With Endogenous Overexpression of MRP2 in Caco-2 and PANC-1 Cells

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aut.relation.articlenumber1330en_NZ
aut.relation.issue9en_NZ
aut.relation.journalCancersen_NZ
aut.relation.volume11en_NZ
aut.researcherDrabsch, Julie
dc.contributor.authorBiswas, Ren_NZ
dc.contributor.authorBugde, Pen_NZ
dc.contributor.authorHe, Jen_NZ
dc.contributor.authorMerien, Fen_NZ
dc.contributor.authorLu, Jen_NZ
dc.contributor.authorLiu, DXen_NZ
dc.contributor.authorMyint, Ken_NZ
dc.contributor.authorLiu, Jen_NZ
dc.contributor.authorMcKeage, Men_NZ
dc.contributor.authorLi, Yen_NZ
dc.date.accessioned2019-11-12T02:08:09Z
dc.date.available2019-11-12T02:08:09Z
dc.date.copyright2019en_NZ
dc.date.issued2019en_NZ
dc.description.abstractOur recent publications showed that multidrug resistance protein 2 (MRP2, encoded by the ABCC2 gene) conferred oxaliplatin resistance in human liver cancer HepG2 cells. However, the contribution of MRP2 to oxaliplatin resistance remains unclear in colorectal and pancreatic cancer lines. We investigated the effects of silencing MRP2 by siRNA on oxaliplatin accumulation and sensitivity in human colorectal cancer Caco-2 cells and pancreatic cancer PANC-1 cells. We characterized the effects of oxaliplatin on MRP2 ATPase activities using membrane vesicles. Over-expression of MRP2 (endogenously in Caco-2 and PANC-1 cells) was associated with decreased oxaliplatin accumulation and cytotoxicity, but those deficits were reversed by inhibition of MRP2 with myricetin or siRNA knockdown. Silencing MRP2 by siRNA increased oxaliplatin-induced apoptotic rate in Caco-2 and PANC-1 cells. Oxaliplatin stimulated MRP2 ATPase activity with a concentration needed to reach 50% of the maximal stimulation (EC50) value of 8.3 ± 0.7 µM and Hill slope 2.7. In conclusion, oxaliplatin is a substrate of MRP2 with possibly two binding sites, and silencing MRP2 increased oxaliplatin accumulation and cytotoxicity in two widely available gastrointestinal tumour lines (PANC-1 and Caco-2).en_NZ
dc.identifier.citationCancers, 11(9), 1330. MDPI AG. Retrieved from http://dx.doi.org/10.3390/cancers11091330
dc.identifier.doi10.3390/cancers11091330en_NZ
dc.identifier.issn2072-6694en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/12990
dc.languageengen_NZ
dc.publisherMDPI AGen_NZ
dc.relation.urihttps://www.mdpi.com/2072-6694/11/9/1330
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.accessrightsOpenAccessen_NZ
dc.subjectGastrointestinal canceren_NZ
dc.subjectMultidrug resistance protein 2 (MRP2)en_NZ
dc.subjectOxaliplatinen_NZ
dc.titleTransport-mediated Oxaliplatin Resistance Associated With Endogenous Overexpression of MRP2 in Caco-2 and PANC-1 Cellsen_NZ
dc.typeJournal Article
pubs.elements-id363671
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Health & Environmental Science
pubs.organisational-data/AUT/Health & Environmental Science/Applied Science
pubs.organisational-data/AUT/Health & Environmental Science/Interprofessional Health
pubs.organisational-data/AUT/Health & Environmental Science/School of Science
pubs.organisational-data/AUT/PBRF
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences/HA Science 2018 PBRF
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences/HI Interprofessional 2018 PBRF
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