4.5 Article

Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells

Journal

ONCOLOGY REPORTS
Volume 33, Issue 1, Pages 157-162

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3600

Keywords

stomach carcinoma; gastric cancer; aerobic glycolysis; LDH-A; oxamate

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Funding

  1. National Natural Science Funding of China [81172366]
  2. Fundamental Research Funds for the Central Universities [lzujbky-2012-224]
  3. Gansu Special Program for High Technology Research and Development [0912TCYA027]

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Lactate dehydrogenase A (LDH-A), which regulates glycolytic flux by catalyzing pyruvate to lactate in the cytoplasm, is believed to be one of the highly attractive therapeutic targets for cancers. Firstly, we detected the expression of LDH-A in gastric cancer (GC) cells. LDH-A inhibitor oxamate was then used to suppress the LDH-A activity in GC cells. Cell proliferation, lactic acid production, Transwell migration assay and apoptosis were assessed, respectively. The results showed that inhibition of LDH-A by oxamate decreased the lactate production. In the presence of glucose, oxamate inhibited cell proliferation in a dose-dependent manner. Flow cytometry assay further confirmed a pro-apoptotic effect of oxamate, and this was likely through increased expression of Bax, activated caspase-3, and decreased expression of Bcl-2. Therefore, we believe that oxamate inhibits cell growth, suppresses tumor invasion, and induces apoptosis in GC cells. LDH-A may be a potential therapeutic target for GC.

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