ANTINEOPLASTIC MULTI-DRUG CHEMOTHERAPY TO SENSITIZE TUMORS TRIGGERS MULTI-DRUG RESISTANCE AND INHIBITS EFFICIENCY OF MAINTENANCE TREATMENT IN GLIOBLASTOMA CELLS

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dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorErdogan, Suat
dc.contributor.authorDelen, Emre
dc.date.accessioned2024-06-12T11:02:41Z
dc.date.available2024-06-12T11:02:41Z
dc.date.issued2022
dc.departmentTrakya Üniversitesien_US
dc.description.abstractCombinations of the well-known antineoplastic agents 5-fluorouracil (5-Fu), cisplatin, and paclitaxel are employed to increase radiotherapy/immunotherapy efficacy against persistent and resistant tumors. However, data remains needed on the hormetic, chronic, and long-term side effects of these aggressive combination chemotherapies. Here we investigated cellular and molecular responses associated with these combined agents, and their potential to induce multi-drug resistance against the temozolomide (TMZ) and etoposide (EP) used in glioblastoma mainte-nance treatment. We analyzed resistance and survival signals in U87 MG cells using molecular probes, fluorescent staining, qRT-PCR, and immunoblot. Repeated treatment with combined 5-Fu, cisplatin, and paclitaxel induced cross-resistance against TMZ and EP. Resistant cells exhibited elevated gene/protein expression of MRP1/ABCC1, ABCC2, BRCP/ABCG2, and GST. Moreover, they managed oxidative stress, cell cycle, apopto-sis, and autophagy signaling to ensure survival. In these groups TMZ and etoposide efficiency dramatically re-duced. Our result suggests that combined high-dose treatments of classical antineoplastic agents to sensitize tu-mors may trigger multi-drug resistance and inhibit maintenance treatment. When deciding on antineoplastic com-bination therapy for persistent/resistant glioblastoma, we recommend analyzing the long-term hormetic and chronic effects on cross-resistance and multi-drug resistance in primary cell cultures from patients.en_US
dc.description.sponsorshipTrakya Uni- versity Scientific Research Fund; [TUBAP 2017/51]en_US
dc.description.sponsorshipFunding information This study was funded by the Trakya Uni- versity Scientific Research Fund (TUBAP 2017/51) .en_US
dc.identifier.doi10.17179/excli2022-5556
dc.identifier.endpage52en_US
dc.identifier.issn1611-2156
dc.identifier.pmid36660193en_US
dc.identifier.scopus2-s2.0-85145844969en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage35en_US
dc.identifier.urihttps://doi.org/10.17179/excli2022-5556
dc.identifier.urihttps://hdl.handle.net/20.500.14551/21380
dc.identifier.volume22en_US
dc.identifier.wosWOS:000910860300001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherExcli Journal Managing Officeen_US
dc.relation.ispartofExcli Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGlioblastomaen_US
dc.subjectMulti-Drug Resistanceen_US
dc.subjectApoptosisen_US
dc.subjectAutophagyen_US
dc.subjectAngiogenesisen_US
dc.subjectU87 MGen_US
dc.subjectMolecular-Mechanismsen_US
dc.subjectDrug-Resistanceen_US
dc.subjectCanceren_US
dc.subjectHypoxiaen_US
dc.subjectPaclitaxelen_US
dc.subjectAutophagyen_US
dc.subjectTemozolomideen_US
dc.subjectSurvivalen_US
dc.titleANTINEOPLASTIC MULTI-DRUG CHEMOTHERAPY TO SENSITIZE TUMORS TRIGGERS MULTI-DRUG RESISTANCE AND INHIBITS EFFICIENCY OF MAINTENANCE TREATMENT IN GLIOBLASTOMA CELLSen_US
dc.typeArticleen_US

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