TY - JOUR ID - 29065 TI - Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 Y1 - 2014 PY - 2014 VL - 15 IS - 7 SP - 3219 EP - 3226 KW - AGPS KW - Lipid metabolism KW - cancer chemotherapy resistance DO - N2 - Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a majorobstacle. 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 thatsilencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM celllines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis throughreducing 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/AKTsignaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2.β-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate thatAGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells. UR - https://journal.waocp.org/article_29065.html L1 - https://journal.waocp.org/article_29065_ffb7570ae0fe0807aa25d4dd657d0d9b.pdf ER -