[Regulatory effect of integrin alpha5 and beta1 on proliferation inhibition of K562 cells induced by interferon alpha-2b].
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.


CONCLUSIONS
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.
Niu
Zhi-Yun
ZY
Department of Hematology, The Second Hospital, Hebei Medical Univercity, Shijiazhuang, Hebei 050000, P. R. China.
Pan
Ling
L
Zhang
Xue-Jun
XJ
Liu
Ying-Jie
YJ
D000906:Antibodies / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D039482:Integrin alpha5 / Q000276:immunology / Q000378:metabolism*; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins
D000906:Antibodies; D005353:Fibronectins; D039482:Integrin alpha5; D019012:Integrin beta1; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases