Signal pathways of leukemia cell proliferation induced by ouabain

The aim of this study was to investigate the effects of ouabain and some specific signal pathway inhibitors on growth regulation in various kinds of leukemia cell lines and to explore the role of signal pathways participating in proliferation or apoptosis of leukemia cells induced by ouabain.By using MTT,the survival rates of leukemia cell lines were observed after utilizing ouabain and the specific signal pathway inhibitors.The expressions of Na+,K+-ATPase α1 subunit of leukemia cells were evaluated by RT-PCR and Western blot.The results showed that low concentration of ouabain(10 nmol/L)could increase the survival rates of lymphocytic leukemia Jhhan cell line and megakaryocytic leukemia M07e cell line,and could up-regulate the expression of Na+,K+-ATPase α1 subunit.Proliferation of these leukemia cells induced by ouabain could be inhibited by PP2 and PD98059 with different extents.It is concluded that Na+,K+-ATPase plays an important role in signal transductions through binding to CTS(ouabain),and they can activate complex signal pathways regulating the growth of leukemia cells.The proliferation effects of cells promoted by ouabain are mediated by activation of Src kinase and ERK1/2 dependent signaling pathway.