Modifying influence of prolonged action of interferon on phenotypic characteristics of human lung cancer cells in vitro

Kudryavets Yu.I., Bezdenezhnykh N.O., Lukyanova N.Yu., Tregubova N.A., Vorontsova A.L.

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.

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