Downregulation of ABCE1 via siRNA affects the sensitivity of A549 cells against chemotherapeutic agents

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dc.contributor.authorKara, Goknur
dc.contributor.authorTuncer, Sema
dc.contributor.authorTurk, Mustafa
dc.contributor.authorDenkbas, Emir Baki
dc.date.accessioned2020-06-25T18:13:27Z
dc.date.available2020-06-25T18:13:27Z
dc.date.issued2015
dc.departmentKırıkkale Üniversitesi
dc.description.abstractATP-binding cassette E1 (ABCE1) is involved in several biological functions in cancer cells such as tumor proliferation, antiapoptotic pathway and chemoresistance mechanism. This work aimed to investigate the alterations in chemosensitivity of A549 lung cancer cells for 5-Fluorouracil (5-FU) and irinotecan by silencing ABCE1 using specific small interfering RNAs (siRNA). The cells were treated with low doses of drugs, alone and also their combinations with ABCE1 siRNA. Cytotoxicity, cell proliferation and apoptosis/necrosis evaluations were performed in order to examine the effects of the combined treatment. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the downregulation of ABCE1. We also investigated the levels of B cell lymphoma 2 (Bcl-2) and mammalian target of rapamycin (mTOR) after the treatments by RT-PCR. Downregulation of ABCE1 improved the anticancer effects of 5-FU in inducing cell viability/proliferation inhibition and apoptosis/necrosis, whereas interestingly, almost did not change or slightly reduced the anticancer effects of irinotecan. ABCE1 expression significantly decreased by transfecting the cells with ABCE1 siRNA. Moreover, Bcl-2 and mTOR levels changed after the single or combined therapy in parallel with the apoptotic and antiproliferation effect. In conclusion, the simultaneous treatment of lung cancer cells with ABCE1 siRNA and 5-FU exhibited synergistic or additive effects; however, ABCE1 siRNA and irinotecan had unexpected antagonistic effects. Our findings demonstrate that the strategy of downregulation of ABCE1 may be included in conventional 5-FU chemotherapy for lung cancer, minimizing the usage of 5-FU at high dosages.en_US
dc.description.sponsorshipHacettepe University, Scientific Research Projects Coordination UnitHacettepe University [968]en_US
dc.description.sponsorshipThis work was financially supported by Hacettepe University, Scientific Research Projects Coordination Unit (Grant No. 968).en_US
dc.identifier.citationclosedAccessen_US
dc.identifier.doi10.1007/s12032-015-0557-3
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue4en_US
dc.identifier.pmid25744244
dc.identifier.scopus2-s2.0-84924176017
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s12032-015-0557-3
dc.identifier.urihttps://hdl.handle.net/20.500.12587/6197
dc.identifier.volume32en_US
dc.identifier.wosWOS:000351474100017
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherHumana Press Incen_US
dc.relation.ispartofMedical Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectABCE1en_US
dc.subjectCombined cancer therapyen_US
dc.subjectDrug resistanceen_US
dc.subject5-FU, irinotecanen_US
dc.subjectSmall interfering RNAen_US
dc.titleDownregulation of ABCE1 via siRNA affects the sensitivity of A549 cells against chemotherapeutic agentsen_US
dc.typeArticle

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