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

Gen Physiol Biophys. 2009 Sep;28(3):294-301. doi: 10.4149/gpb_2009_03_294.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Alkaline Phosphatase / 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*
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • ATP-Binding Cassette Transporters
  • Interferon-alpha
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase