Study on the biological activity and molecular mechanism of IFNalpha on human myeloma cell line Sko-007.
- Author:
Lun SONG
1
;
Yan LI
;
Yingxun SUN
;
Beifen SHEN
Author Information
- Publication Type:Journal Article
- MeSH: Antigens, CD; drug effects; metabolism; Cell Cycle; drug effects; Cell Division; drug effects; Cytokine Receptor gp130; Dose-Response Relationship, Drug; Down-Regulation; Enzyme Activation; drug effects; G1 Phase; drug effects; Humans; Immunoblotting; Interferon-alpha; pharmacology; Membrane Glycoproteins; drug effects; metabolism; Mitogen-Activated Protein Kinases; metabolism; Multiple Myeloma; metabolism; pathology; Proto-Oncogene Proteins c-bcl-2; metabolism; Receptors, Interleukin-6; drug effects; metabolism; Resting Phase, Cell Cycle; drug effects; S Phase; drug effects; Tumor Cells, Cultured; drug effects; metabolism; bcl-X Protein
- From: Chinese Journal of Hematology 2002;23(10):517-519
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the biological activity and molecular mechanism of interferon alpha (IFNalpha) on human myeloma cell line Sko-007.
METHODSThe effect of IFNalpha on the growth of Sko-007 cells was measured by MTT assay. Cells cycle distribution and the expression of two IL-6 receptor chains (IL-6R and gp130) on Sko-007 cell surface in the absence or presence of IFNalpha were monitored by FACS analysis. The activation state of protein kinase ERK, which is involved in Ras/MAPK signal transduction pathway mediating cell survival and proliferation, and the expression of anti-apoptotic Bcl-2 family proteins-Bcl-2, Bcl-x(L) and Mcl-1 in Sko-007 cells with or without IFNalpha were determined by immunoblot assay.
RESULTIFNalpha arrested Sko-007 cell cycle progression. After stimulation with IFNalpha, an obvious increase in G(0)/G(1) phase (41.1%-->84.1%) and decrease in S phase (57.1%-->13.3%) of Sko-007 cell cycle distribution can be observed. Moreover, the proliferation of Sko-007 cells was dramatically inhibited in the presence of IFNalpha, with a maximal inhibitory rate up to 88%. In addition, the expression of gp130 on cell surface, the activation of protein kinase ERK and the expression of Bcl-2 and Bcl-x(L) were all down-regualted in IFNalpha-stimulated Sko-007 cells.
CONCLUSIONThe inhibitory effect of IFNalpha on the proliferation of Sko-007 cells was mediated by gp130 down-regulation, degradation of Bcl-2 family anti-apoptotic proteins and inhibition of ERK activation.