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 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.
Krejcová
Daniela
D
Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
Procházková
Jirina
J
Kubala
Lukás
L
Pacherník
Jirí
J
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology / Q000503:physiopathology*; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology / Q000503:physiopathology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase