Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4

Many tumors metabolise the majority of the glucose that they take up through glycolysis even in the presence of an adequate oxygen supply. Lactate dehydrogenase A (LDH-A) is the critical enzyme that catalyses the transformation of pyruvate to lactate. We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo. A statistical analysis of 661 ITGC specimens showed a significant correlation between LDH-A and Oct4 expression. Moreover, patients with low LDH-A/negative Oct4 expression exhibited better overall survival than patients with other combinations. We conclude that the close correlation of LDH-A and Oct4 may offer a promising therapeutic strategy for ITGC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.