Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells
Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells
复制标题
抑制乳酸脱氢酶A对人胃癌细胞生长和侵袭的影响。
DOI：
10.3892/or.2014.3600
复制
发表时间：
2015-01-01
期刊：
影响因子：
4.2
通讯作者：
Qiao, Liang
中科院分区：
文献类型：
--
作者：
Liu, Xiaojun;Yang, Zhongxia;Qiao, Liang
乳酸脱氢酶A（LDH-A）是一种在细胞质中通过催化丙酮酸转化为乳酸来调节糖酵解的酶，被认为是肿瘤治疗的重要靶点之一。首先，我们检测了LDH-A在胃癌细胞中的表达。然后使用LDH-A抑制剂草胺酸来抑制GC细胞中的LDH-A活性。分别检测细胞增殖、乳酸生成、Transwell迁移实验和细胞凋亡。结果表明，草氨酸抑制乳酸脱氢酶A的活性会降低乳酸的产量。在葡萄糖存在下，草氨酸盐以剂量依赖性方式抑制细胞增殖。流式细胞术分析进一步证实了草酸酯的促凋亡作用，这可能是通过增加Bax的表达，激活caspase-3，并降低Bcl-2的表达。因此，我们认为，草酸盐抑制细胞生长，抑制肿瘤侵袭，并诱导胃癌细胞凋亡。LDH-A可能是胃癌潜在的治疗靶点。
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.