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

Treatments of non-small cell lung cancer (NSCLC), the most common form of lung cancer, still remain poor. Interferon alpha (IFN-alpha), an important physiological immunomodulator, possesses direct cytotoxic and cytostatic effects on tumour cells, antiangiogenic effects, and activates anti-tumour imm...

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Published in:General physiology and biophysics 2009-09, Vol.28 (3), p.294-301
Main Authors: Krejcová, Daniela, Procházková, Jirina, Kubala, Lukás, Pacherník, Jirí
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
ATP-Binding Cassette Transporters - metabolism
Carcinoma - enzymology
Carcinoma - physiopathology
Cell Cycle - physiology
Cell Differentiation - physiology
Cell Line, Tumor
Cell Proliferation
Cell Survival - physiology
Humans
Interferon-alpha - metabolism
Lung Neoplasms - enzymology
Lung Neoplasms - physiopathology
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Signal Transduction
STAT1 Transcription Factor - metabolism
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Summary:Treatments of non-small cell lung cancer (NSCLC), the most common form of lung cancer, still remain poor. Interferon alpha (IFN-alpha), an important physiological immunomodulator, possesses direct cytotoxic and cytostatic effects on tumour cells, antiangiogenic effects, and activates anti-tumour immunity. Recently, the IFN-alpha oncologic indications have included melanoma, renal carcinoma, and different types of leukaemia. However, the application of IFN-alpha 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-alpha 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-alpha significantly inhibited the proliferation of A549 cells which was not connected with arrest in a particular cell cycle phase. Further, IFN-alpha-mediated differentiation of A549 was observed based on an increase in alkaline phosphatase activity. Simultaneously, IFN-alpha increased the expression and activity of ATP-transporters mediating MDR. Thus, the IFN-alpha 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-alpha as a therapeutic agent for NSCLC.
ISSN:0231-5882
DOI:10.4149/gpb_2009_03_294