Gemcitabine/Cisplatin Treatment Induces Concomitant SERTAD1, CDKN2B and GADD45A Modulation and Cellular Changes in Bladder Cancer Cells Regardless of the Site of TP53 Mutation

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dc.contributor.authorda Silva, Glenda Nicioli
dc.contributor.authorFiloni, Leandro Toshio
dc.contributor.authorSalvadori, Maria Cecília
dc.contributor.authorSalvadori, Daisy Maria Fávero [UNESP]
dc.contributor.institutionUFOP – Federal University of Ouro Preto
dc.contributor.institutionUFOP – Universidade Federal de Ouro Preto
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T17:32:42Z
dc.date.available2018-12-11T17:32:42Z
dc.date.issued2018-04-01
dc.description.abstractSimultaneous use of cisplatin (CIS) and gemcitabine (GEN) for treating bladder cancer has increased because of their complementary effects. However, the molecular mechanisms underlying the activities of these two antineoplastic drugs are not fully known. Here, molecular biology techniques and microscopy were used to investigate transcriptomic and morphological changes in low and high-grade urinary bladder transitional carcinoma cell lines [RT4 - wild type TP53; 5637 - two TP53 mutations, one in codon 72 (Arg-Pro) and other in codon 280 (Arg-Thr) and T24 - in-frame deletion of tyrosine 126 in the TP53 allele] simultaneously treated with CIS/GEN. Gene expression profile was evaluated by PCR arrays; cell morphology by scanning and transmission electron microscopy, and apoptosis was analyzed using fluorescent dye. Results showed concomitantly upregulation of CDKN2B (G1/S transition), GADD45A (DNA repair and apoptosis) and SERTAD1 (regulation of transcription) gene, increased number of nuclear chamfers and apoptotic cells, and reduced number of microfilaments, organelles and in the size of the nucleus in 5637 and T24 cells after simultaneous treatment with CIS/GEN. In conclusion, independently of the TP53 mutation status and tumor grade, CIS/GEN induced gene modulation accompanied by changes in cell morphologies, which confirm the antiproliferative activity of the treatment protocol. These findings help to understand the pathways modulated by these antineoplastic agents and may provide insights for anti-cancer chemotherapy.en
dc.description.affiliationSchool of Pharmacy UFOP – Federal University of Ouro Preto
dc.description.affiliationEscola de Farmácia Departamento de Análises Clínicas UFOP – Universidade Federal de Ouro Preto
dc.description.affiliationInstitute of Physics USP – University of São Paulo
dc.description.affiliationMedical School UNESP – State University of São Paulo
dc.description.affiliationUnespMedical School UNESP – State University of São Paulo
dc.format.extent407-417
dc.identifierhttp://dx.doi.org/10.1007/s12253-017-0255-x
dc.identifier.citationPathology and Oncology Research, v. 24, n. 2, p. 407-417, 2018.
dc.identifier.doi10.1007/s12253-017-0255-x
dc.identifier.file2-s2.0-85020064231.pdf
dc.identifier.issn1532-2807
dc.identifier.issn1219-4956
dc.identifier.scopus2-s2.0-85020064231
dc.identifier.urihttp://hdl.handle.net/11449/178919
dc.language.isoeng
dc.relation.ispartofPathology and Oncology Research
dc.relation.ispartofsjr0,751
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectBladder cancer
dc.subjectCell morphology
dc.subjectChemotherapy
dc.subjectCisplatin
dc.subjectGemcitabine
dc.subjectGene expression
dc.titleGemcitabine/Cisplatin Treatment Induces Concomitant SERTAD1, CDKN2B and GADD45A Modulation and Cellular Changes in Bladder Cancer Cells Regardless of the Site of TP53 Mutationen
dc.typeArtigo

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