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Signal pathways in ouabain-induced proliferation of leukemia cells

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Abstract

Background

Cardiotonic steroids (CTSs) can bind to Na+/K+-ATPase and activate protein kinase cascades, resulting in changes in cell proliferation, differentiation or apoptosis in a cell-specific manner. We explored the participation of ouabain-activated signaling pathways in growth regulation of leukemia cells.

Methods

Lymphocytic leukemia Jhhan cells and megakaryocytic leukemia M07e cells were incubated at different concentrations of ouabain (0, 1 and 10 nmol) for 24 hours. Cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay. To probe the role of ouabain-induced signaling in control of cell growth, we employed Src kinase inhibitor PP2 and the MEK inhibitor PD98059, respectively. The expression of Na+/K+-ATPase α1 subunit of leukemia cells was evaluated by RT-PCR and Western blotting.

Results

One nmol and 10 nmol ouabain promoted proliferation of both Jhhan and M07e cells. Ouabain also up-regulated the expression of Na+/K+-ATPase α1 subunit. Addition of either PP2 or PD98059 blocked the effects of ouabain on cell proliferation.

Conclusion

Ouabain activates Src and ERK1/2 pathways and regulates the proliferation of leukemia cells.

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Authors and Affiliations

  1. Pediatric Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Jia-Wei Xu, Run-Ming Jin, En-Qin Li, Yan-Rong Wang & Yan Bai

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  1. Jia-Wei Xu
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  2. Run-Ming Jin
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  3. En-Qin Li
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  4. Yan-Rong Wang
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  5. Yan Bai
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Correspondence to Run-Ming Jin.

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Xu, JW., Jin, RM., Li, EQ. et al. Signal pathways in ouabain-induced proliferation of leukemia cells. World J Pediatr 5, 140–145 (2009). https://doi.org/10.1007/s12519-009-0028-z

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  • DOI: https://doi.org/10.1007/s12519-009-0028-z

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