Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells.
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.
Department of Medical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
Xiaojun
X
Liu
Department of Infection, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
Zhongxia
Z
Yang
Key Laboratory for Gastrointestinal Disease of Gansu Province, Lanzhou, Gansu, P.R. China.
Zhaofeng
Z
Chen
Department of Medical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
Rui
R
Chen
Department of Medical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
Da
D
Zhao
Key Laboratory for Gastrointestinal Disease of Gansu Province, Lanzhou, Gansu, P.R. China.
Yongning
Y
Zhou
Storr Liver Unit, Westmead Millennium Institute, Western Clinical School of the Faculty of Medicine at Westmead Hospital, The University of Sydney, Westmead, NSW, Australia.
Liang
L
Qiao
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D010072:Oxamic Acid / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*
D000970:Antineoplastic Agents; D007527:Isoenzymes; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D010072:Oxamic Acid