›› 2018, Vol. 38 ›› Issue (11): 1294-.doi: 10.3969/j.issn.1674-8115.2018.11.004

• Original article (Basic research) • Previous Articles     Next Articles

Mechanism of HIF-1α-PDK1 signaling system involved in glucose metabolism and drug resistance in acute monocytic leukemia

XU Xiao-wei, ZHAO Chu-xian, LI Su, WANG Chun, SONG Xian-min, BAI Hai-tao   

  1. Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
  • Online:2018-11-28 Published:2018-12-15
  • Supported by:
    Scientific Research Project of Shanghai Municipal Commission of Health and Family Planning, 201440292

Abstract: Objective · To investigate the mechanism of HIF-1α-PDK1 signaling system mediated glucose metabolism and drug resistance in acute monocytic leukemia cells. Methods · The of pyruvate dehydrogenase kinase 1 (PDK1) mRNA in U937, U937/DNR and acute monocytic leukemia cells was detectedquantitative polymerase chain reaction (qPCR). siRNA HIF-1α plasmid was constructed and transferred to U937 and U937/ DNR cells for 24 hgene silencing. Cell proliferation inhibition was examinedMTT assay. The level of PDK1 mRNA was detectedqPCR, and the of PDK1 and multi-drug resistance gene 1 (MDR1) proteins was detectedWestern blotting. Cell membrane potential was measuredflow cytometry using JC-1. Lactic acid level in the culture fluid was determinedblood gas analyzer. Dichloroacetate (DCA) and daunorubicin (DNR) were added to treat U937/DNR and acute monocytic leukemia cells for 24 h, MTT was used to calculate cell proliferation inhibition and Western blotting was used to estimate the of PDK1 and MDR1 proteins. Results · PDK1 mRNA was highly expressed in U937, U937/DNR and acute monocytic leukemia cells. Silencing hypoxia-inducible factor-1α (HIF-1α) significantly inhibited the proliferation activity, PDK1 and MDR1 and lactic acid production in U937 and U937/DNR cells. DCA could reverse the resistance to DNR in U937/DNR and relapsed acute monocytic leukemia cells. Conclusion · HIF-1α-PDK1 signaling system may regulate glucose metabolism and participate in the drug resistance of acute monocytic leukemia.

Key words: pyruvate dehydrogenase kinase 1 (PDK1), multidrug resistance, hypoxia-inducible factor-1&, alpha, (HIF-1&, alpha, ), acute monocytic leukemia

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