Drug resıstance restrıcts the effıcacy of short term low dose mıtomycın-c treatment ın umuc-3 bladder cancer cells

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dc.authoridGul, Murat -- 0000-0002-6657-6227
dc.contributor.authorGül, Murat
dc.contributor.authorGöktaş, Serdar
dc.contributor.authorDemirel Kars, Meltem
dc.contributor.authorKaynar, Mehmet
dc.date.accessioned13.07.201910:50:10
dc.date.accessioned2019-07-16T09:16:51Z
dc.date.available13.07.201910:50:10
dc.date.available2019-07-16T09:16:51Z
dc.date.issued2018
dc.departmentTıp Fakültesi
dc.description.abstractOBJECTIVE: Mitomycin-c (MMC) is the most used intravesical adjuvant agent in non-muscle invasive bladder cancer to prevent recurrence. However, a consensus on about appropriate dosage and treatment schedule of MMC is lacking. We, therefore, aimed to evaluate the most appropriate MMC dosage using an in vitro model of high-grade human bladder cancer. METHODS: UMUC-3 cells, a model for high-grade bladder cancer, were exposed to MMC in different time courses to assess its toxicological effects. XTT cell proliferation kit was used to evaluate the effect of MMC on the proliferation of UMUC-3 cell line. Gene expression analysis for the MDR1, BCL2 and ANXA5 genes was performed by Real-time PCR and flow cytometry analysis were conducted to evaluate the cell death mechanism and acquired resistance after MMC exposure. An ANXA5 kit was used to detect apoptotic cells, and 7-AAD was used to detect necrotic cells. RESULTS: Cell proliferation was prevented to a large extent (IC50, 0.175-0.081 mg/mL) and cytotoxic effects were observed after 5 mu g/mL and 10 mu g/mL MMC administrations for 1 and 2-h, after the 4th and 2nd dose cycles, respectively. Moreover, cell death was observed at 5 mu g/mL and 10 mu/mL MMC applications for 1-h and 2-h by the sixth and second week, respectively. Flow cytometry exhibits increased subpopulation of drug-extruding UMUC-3 cells after a single dose of MMC for 1-h. MMC did not increase the number of apoptotic or necrotic cells; yet, MDR1 (multiple drug resistance) and ANXA5 (apoptotic) expression levels were increased and BCL2 (anti-apoptotic) expression was decreased. Limitations: In-vitro nature of the study and working with only one cell culture are inherit limitations of this project. CONCLUSION: A single dose of MMC administration for 1 or 2-h results in drug-resistance. If maintenance treatment is administered for one hour, it should be continued throughout a 6-week period.
dc.description.sponsorshipSelcuk University, Scientific Research Projects (SUSRP) [13102031]
dc.description.sponsorshipThis study was supported by Selcuk University, Scientific Research Projects (SUSRP) (project number: 13102031).
dc.identifier.endpage793en_US
dc.identifier.issn0004-0614
dc.identifier.issn1576-8260
dc.identifier.issue9en_US
dc.identifier.pmid30403381
dc.identifier.scopusqualityQ3
dc.identifier.startpage783en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12451/4662
dc.identifier.volume71en_US
dc.identifier.wosWOS:000457818300007
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherInıestares, S.A.
dc.relation.ispartofArchıvos Espanoles de Urologıa
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectBladder Cancer
dc.subjectMulti-drug Resistance
dc.subjectMitomycin-c
dc.subjectFlow Cytometry
dc.subjectUMUC-3
dc.titleDrug resıstance restrıcts the effıcacy of short term low dose mıtomycın-c treatment ın umuc-3 bladder cancer cells
dc.typeArticle

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