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PO3-7-21

Beta-elemene inhibits glycolysis leading to suppression of breast cancer metastasis dependent on blocking nuclear import of PKM2 and GLUT1 expression

[Speaker] Wenxing Chen:1
[Co-author] Yin Lu:1
1:School of Pharmacy, and Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, China

Metastasis is the most important factor for high lethality in clinic. And more and more evidences proved that metastasis is tightly associated with energy metabolism with increased glycolysis and glucose uptake. This study was to determine anti-metastatic effect of chinese traditional medicine, β-elemene, on breast cancer and its possible metabolic mechanism. The data indicates that β-elemene could obviously inhibit the migration, invasion and angiogenesis of MDA-MB-231 and MCF-7 cells in vitro. And β-elemene in vitro could significantly inhibite the process of glycolysis, decrease the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase (PK) activity. Moreover, 20mg and 50mg/kg β-elemene could remarkably inhibit the lung and liver metastasis of high and low metastatic breast cancer, but selectively influence the metabolism of the lung and liver metastatic foci of different metastasic model animals.HPLC-MS, western blot and immunofluotescence further revealed that β-element suppressed glycolysis through regulating the nuclear transportation of PKM2 and the expression glycosis through regulating the nuclear transportation of PKM2 and the expression of GLUT1, MCT1, MCT4 and LDHA, conseqnuently, inhibited the metastasis of breast cancer. Conclusively, β-elemene inhibits glycolysis leading to suppression of breast cancer metastasis dependent on blocking nuclear import of PKM2 and GLUT1 expression.
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