Background & objective: Integrin beta1 can inhibit the proliferation of chronic myelocytic leukemia (CML) ph+ cells. The dysfunction of integrin beta1 might accelerate the growth of CML ph+ cells. This study was to explore the effects of integrin alpha5 and beta1 on the proliferation inhibition of K562 cells induced by IFNalpha-2b.
Methods: The expression indexes of integrin alpha5 and beta1 on K562 cells, the binding capability of K562 cells to fibronectin (FN), and K562 cell-FN binding blocking induced by integrin alpha5 and beta1 antibodies were evaluated by flow cytometry (FCM). The viability of K562 cells, treated with IFNalpha-2b (10,000 u/ml), was observed by MTT assay. The mRNA level of focal adhesion kinase (FAK) in K562 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) 48 h after treatment of interferon alpha-2b (IFNalpha-2b).
Results: The positive rates of integrin alpha5 and beta1 were significantly higher on K562 cells than on bone marrow mononuclear cells from healthy donors [(97.59+/-1.04)% vs. (64.05+/-2.38)%, (99.24+/-0.52)% vs. (72.40+/-3.56)%, P<0.05). IFNalpha-2b could not change the expression of integrin alpha5 and beta1 on K562 cells, but improved the binding capability of K562 cells to FN, which could be blocked by anti-alpha5 and/or anti-beta1 antibodies. IFNalpha-2b enhanced the expression of FAK gene, and inhibited the proliferation of K562 cells. The anti-alpha5 and anti-beta1 antibodies improved the inhibitory effect of IFNalpha-2b on the proliferation of K562 cells, and blocked IFNalpha-2b-induced increase of FAK gene expression.
Conclusion: IFNalpha-2b could inhibit the proliferation of K562 cells through restoring the function of integrin alpha5 and beta1, enhancing binding capability of integrin alpha5 and beta1 to FN, and up-regulating FAK gene expression.