Assuntos
Transição Epitelial-Mesenquimal , Interferons/metabolismo , Neoplasias/fisiopatologia , Animais , Desdiferenciação Celular , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
AIM: To estimate the effect of long-term IFN treatment of human non-small-cell lung cancer cell line A-549 on their karyotype characteristics and on the clonal structure of cell population. METHODS: Cytogenetic research was performed by standard methods using routine and differential staining. Cytogenetic characteristics were estimated per 1000 cells (ppm, (per thousand)). RESULTS: Cytogenetic analysis of IFN-modified A-549 human lung cancer cells had demonstrated far-going changes in their population structure. It was shown that long term cultivation with IFN altered the chromosome modal class of A-549 cells, induced the domination of hromosomes with certain molecular markers: the number of metaphases with der (6) t (6; 1) chromosomal rearrangement increased significantly (from 6% to 80%, p CONCLUSION: Long-term IFN effect results in alterations of cytogenetic properties of A-549 human lung cancer cells.
Assuntos
Adenocarcinoma/genética , Aberrações Cromossômicas/induzido quimicamente , Interferon-alfa/farmacologia , Neoplasias Pulmonares/genética , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Bandeamento Cromossômico , Cromossomos Humanos Par 1 , Avaliação Pré-Clínica de Medicamentos , Humanos , Cariotipagem , Neoplasias Pulmonares/patologia , Fatores de Tempo , Translocação Genética , Células Tumorais CultivadasRESUMO
AIM: To study modifying influence of interferon (IFN) on some phenotypic properties of human non-small-cell lung cancer cells (NSCLC) upon prolonged exposition of the cells with IFN. MATERIALS AND METHODS: A-549 cells were cultivated with IFN at increasing concentrations for a long period of time (up to 1 year). Cell morphology and ultrastructure were studied by light and electron microscopy. Expression of adhesion protein E-cadherin, and vimentin, cytosceleton protein associated with tumor cell migration and invasion, antigen of proliferating cells Ki-67, angiogenesis-stimulating protein VEGF were studied using the method of immunocytochemistry. Autonomity of the cell growth was studied with the use of colony formation in soft agar, platting efficiency assay, and growth in serum-free medium. RESULTS: It has been shown that prolonged action of IFN results in significant and irreversible inhibition of manifestation of malignant phenotype: decreased of proliferative potential and inhibited autonomy of the cells; in complicated cell ultrastructure; in decreased expression vimentin and in increased expression of E-cadherin. Also, an inhibiting influence of IFN on expression of EGF receptors and VEGF in tumor cells have been shown. CONCLUSIONS: The data are showing that prolonged exposition of NSCLC cells to IFN is accompanied by stable phenotypic alterations of the cells directed on significant loss of malignancy and their shift to more differentiated phenotype.
