Modulation of cell proliferation and differentiation of human lung carcinoma cells by the interferon-alpha

Abstract

Treatments of non-small cell lung cancer (NSCLC), the most common form of lung cancer, still remain poor. Interferon alpha (IFN-α), an important physiological immunomodulator, possesses direct cytotoxic and cytostatic effects on tumour cells, antiangiogenic effects, and activates anti-tumour immunity. Recently, the IFN-α oncologic indications have included melanoma, renal carcinoma, and different types of leukaemia. However, the application of IFN-α in therapy of lung cancer has not been validated yet. Herein the human lung carcinoma cell line A549, a model of NSCLC in vitro, was used to pursue the effect of IFN-α on A549 cell proliferation and differentiation together with the effect on protein expression and activity of three ATP-transporters mediating multi-drug resistance (MDR). IFN-a significantly inhibited the proliferation of A549 cells which was not connected with arrest in a particular cell cycle phase. Further, IFN-a-mediated differentiation of A549 was observed based on an increase in alkaline phosphatase activity. Simultaneously, IFN-a increased the expression and activity of ATP-transporters mediating MDR. Thus, the IFN-a down-regulation of NSCLC cell proliferation was accompanied by a potential of cells to exclude potential therapeutic substances such as chemotherapeutic agents. These effects could have a significant impact on considerations of IFN-α as a therapeutic agent for NSCLC.