Anticancer effect of XAV939 is observed by inhibiting lactose dehydrogenase A in a 3?dimensional culture of colorectal cancer cells > REFERENCE LIBRARY

Abstract

XAV939, a tankyrase inhibitor, exerts an anticancer effect in 3?dimensional (3D) cultured SW480 cells, however this is not exhibited in 2?dimensional (2D) cultured SW480 cells. In the current study, XAV939 induced a 3.7?fold increase in cellular apoptosis in 3D culture but not in the 2D culture. However, no significant changes were indicated in cell cycle distribution in the 2D or 3D culture. Based on the observation that protein expression, which was associated with the glycolytic pathway, was increased in the 3D culture, the effect of XAV939 on the patterns of glycolytic protein expression was assessed. XAV939 was revealed to decrease lactose dehydrogenase A (LDHA) expression in 3D cultured SW480 cells, but only exerted a small effect in the 2D culture. The coadministration of XAV939 with the LDHA inhibitor FX11 decreased proliferation in 3D cultured SW480 cells compared with the single administration of FX11, while there was no additive effect in the 2D culture. The lactate assay also indicated that XAV939 decreased lactate secretion in the 3D cell culture but not in the 2D culture. These results suggest that XAV939 exerts an anticancer effect through inhibition of LDHA in the 3D culture.