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Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

  • Zhu, Yu (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration) ;
  • Liu, Xing-Jun (Department of Neurosurgery, Tianjin Haihe Hospital) ;
  • Yang, Ping (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration) ;
  • Zhao, Meng (Department of Immunology and Department of Biochemistry, School of Basic Medical Sciences, Tianjin Medical University) ;
  • Lv, Li-Xia (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration) ;
  • Zhang, Guo-Dong (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration) ;
  • Wang, Qin (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration) ;
  • Zhang, Ling (Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration)
  • Published : 2014.04.01

Abstract

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

Keywords

AGPS;Lipid metabolism;cancer chemotherapy resistance

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