title: 5-Fluorouracil potentiates the anti-cancer effect of oxaliplatin on Colo320 colorectal adenocarcinoma cells.
abstract: BACKGROUND & AIMS. The present study was designed to examine the combined effects of Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) in the Colo320 cell line. METHODS. The antiproliferative effects were evaluated using the MTT assay, apoptosis by flow cytometry, and RT-PCR-array technology was used to determine the major effects of the two chemotherapeutic drugs upon the most important genes involved in apoptosis. RESULTS. The antiproliferative effects of the therapeutic agents, as individual therapy or combined, proved to be dose and time-dependent, with increased efficiency for the combined treatment. Flow cytometry data revealed increased apoptotic processes in the case of the combined treatment at 24 hours after administration. The RT-PCR-array data indicated that at 24 hours after OXA treatment, 49 genes were differentially expressed, of which 45 were up-regulated and 4 down-regulated. In the case of the 5-FU treatment, 35 genes were down regulated and 2 up regulated. In the combined treatment of 5-FU and OXA, 19 genes were up-regulated and 15 down-regulated. CONCLUSIONS. This study proved that drug resistance could be counteracted by combining OXA with 5-FU to form a tandem that is capable of reducing cell proliferation and to stimulate extrinsic apoptosis pathway by targeting death receptors on the cell surface.
authors.affiliation: Department of Functional Genomics and Experimental Pathology, Oncological Institute Ion Chiricuta, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.forename: Cornelia
authors.initials: C
authors.lastname: Braicu
authors.forename: Valentina
authors.initials: V
authors.lastname: Pileczki
authors.forename: Roxana
authors.initials: R
authors.lastname: Cojocneanu Petric
authors.forename: Nicolae
authors.initials: N
authors.lastname: Miron
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Balacescu
authors.forename: Dana
authors.initials: D
authors.lastname: Iancu
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil