Abstract 1156: Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells

Abstract

Abstract Glycine decarboxylase (GLDC) is a metabolic oncogene that links glycine metabolism with tumorigenesis. In humans, GLDC is part of a multienzyme complex that couples the decarboxylation of glycine to the biosynthesis of serine. The role of GLDC in relation to chemoresistance is unclear. We designed this study to determine the role of GLDC in chemoresistance in ovarian cancer cells. First, we found GLDC is downregulated in paclitaxel resistant ovarian cancer cells (OVCAR3/PTX). Prompted by decreased glucose transport in OVCAR3/PTX cells, we transplanted OVCAR3 and OVCAR3/PTX onto the back of the NOD-scid IL2Rgammanull mice and found that the OVCAR3/PTX tumor grew less rapidly than paclitaxel sensitive ovarian cancer cells (OVCAR3). We also found that GLDC is downregulated in OVCAR3/PTX tumor. In vitro study revealed that the inhibitory effect of siGLDC on proliferation was significantly greater in OVCAR3 than in OVCAR3/PTX. We also found that knockdown of GLDC in OVCAR3 cells rendered ovarian cancer cells PTX-resistant. Finally, we determined GLDC expressions in patients with chemosensitive and chemoresistant serous type ovarian cancer and found that GLDC expression was markedly downregulated in chemoresistant cancer patients. These results suggest GLDC is associated with ovarian cancer chemoresistance. Citation Format: Jin Young Kim, Sojin Shin, Eunyoung HA, Soondo Cha, Chi-Heum Cho. Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1156.