title: Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration.
abstract: Previous studies have demonstrated that tumor-associated macrophages (TAMs) are pivotal players in tumor progression via modulation of tumor angiogenesis, inflammation, metastasis and oxidative stress, as well as of the response of cancer cells to cytotoxic drugs. Nevertheless, the role of TAMs in the prognosis of colorectal cancer remains controversial. Therefore, the present study aimed to investigate how TAMs mediate the response of C26 colon carcinoma cells to the cytotoxic drug 5-fluorouracil (5-FU), upon TAM co-cultivation with these cancer cellsin vitro. In this respect, 5-FU cytotoxicity was assessed in C26 cells in standard culture and in a co-culture with peritoneal macrophages, the production of NF-κB was determined by western blot analysis, and the production of angiogenic/inflammatory proteins in each experimental model was evaluated by protein array analysis. To gain further evidence of the effect of TAMs on oxidative stress, malondialdehyde was measured through high-performance liquid chromatography, and the total nonenzymatic antioxidant levels and the production of nitrites were measured through colorimetric assays. The results demonstrated that TAMs exerted a dual role in the response of C26 cells to 5-FU administration in the co-culture model. Thus, on one side, TAMs sensitized C26 cells to 5-FU administration through inhibition of the production of inflammatory and angiogenic proteins in these cancer cells; however, they also protected cancer cells against 5-FU-induced oxidative stress. Collectively, the present findings suggest that the combined administration of 5-FU with pharmacological agents that prevent TAMs to maintain the physiological range of tumor cell oxidative stress may highly improve the therapeutic potential of this drug.
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Laura
authors.initials: L
authors.lastname: Patras
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Sesarman
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Emilia
authors.initials: E
authors.lastname: Licarete
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Luca
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Marius Costel
authors.initials: MC
authors.lastname: Alupei
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Rakosy-Tican
authors.affiliation: Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, 400271 Cluj-Napoca, Romania.
authors.forename: Manuela
authors.initials: M
authors.lastname: Banciu
keywords: 5-fluorouracil; angiogenesis; co-culture; colon carcinoma cells; inflammation; tumor-associated macrophages