Search, authorship, and/or publication of this article.FundingThe author(s) disclosed receipt from the following financial assistance for the research, authorship, and/or publication of this article: This function was supported by the Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore (to OKM) and Future Leaders in Discomfort Research, American Discomfort Society (to OKM).
Virag et al. BMC Genomics 2013, 14:480 http://www.biomedcentral.com/1471-2164/14/RESEARCH ARTICLEOpen AccessOxaliplatin induces unique cellular and molecular chemoresistance patterns in colorectal cancer cell lines of identical originsPiroska Virag1, Eva Fischer-Fodor1, Maria Perde-Schrepler1, Ioana Brie1,2, Corina Tatomir1, Loredana Balacescu1, Ioana Berindan-Neagoe1,2, Bogdan Victor1 and Ovidiu BalacescuAbstractBackground: Cancer cells often adopt cellular and molecular alterations and acquire resistance to cytostatic drugs. ChemoUrea Inhibitors Related Products therapy with oxaliplatin is among the top treatment options for colorectal cancer having a response rate of 50 , inducing intrastrand cross-links on the DNA. Despite of this drug’s efficiency, resistance develops in almost all metastatic sufferers. Chemoresistance being of vital value for the drug’s clinical efficiency this study aimed to contribute towards the identification and description of some cellular and molecular alterations induced by prolonged oxaliplatin therapy. Resistance to oxaliplatin was induced in Colo320 (Colo320R) and HT-29 (HT-29R) colorectal adenocarcinoma cell lines by exposing the cells to rising concentrations in the drug. Alterations in morphology, cytotoxicity, DNA cross-links formation and gene expression profiles had been assessed within the parental and Talsaclidine Agonist resistant variants with microscopy, MTT, alkaline comet and pangenomic microarray assays, respectively. Outcomes: Morphology analysis revealed epithelial-to-mesenchymal transition within the resistant vs parental cells suggesting alterations in the cells’ adhesion complexes, by way of which they obtain enhanced invasiveness and adherence. Cytotoxicity measurements demonstrated resistance to oxaliplatin in each cell lines; Colo320 getting more sensitive than HT-29 to this drug (P 0.001). The therapy with oxaliplatin brought on big DNA cross-links in each parental cell lines; in Colo320R small amounts of DNA cross-links had been still detectable, when in HT-29R not. We identified 441 differentially expressed genes in Colo320R and 613 in HT-29R as when compared with their parental counterparts (at the least 1.five -fold up- or down- regulation, p 0.05). More disrupted functions and pathways were detected in HT-29R cell line than in Colo320R, involving genes responsible for apoptosis inhibition, cellular proliferation and epithelial-to-mesenchymal transition. Various upstream regulators had been detected as activated in HT-29R cell line, but not in Colo320R. Conclusions: Our findings revealed a far more resistant phenotype in HT-29R as in comparison with Colo320R and diverse cellular and molecular chemoresistance patterns induced by prolonged therapy with oxaliplatin in cell lines with identical origins (colorectal adenocarcinomas). Key phrases: Oxaliplatin, Colorectal cancer, Chemoresistance, DNA cross-links, Gene expression profile Correspondence: [email protected] Equal contributors 1 The Oncology Institute “Prof.Dr.I. Chiricuta”, 400015 Republicii Str., nr. 34-36, Cluj-Napoca, Romania Full list of author information and facts is obtainable at the finish on the report?2013 Virag et al.; lice.
