摘要：Tetrazanbigen (TNBG), a novel synthetic antitumor drug, may induce the death of cancer cells through a tumor-associated lipoidosis mechanism and result in accumulation of lipid droplets (LDs) in the cytoplasm. In this study, the mechanism underlying the antitumor effects of TNBG was investigated in human hepatocellular carcinoma cell line (QGY-7701 cells). The subcellular proteome of QGY-7701 cells after TNBG treatment was isolated using an established two-dimensional gel electrophoresis (2-DE) technique. Gel images were analyzed by the 2-DE PDQuest software. The differentially expressed proteins were identified by matrix-associated laser desorption ionization time-of-flight mass (MALDI-TOF-MS) spectrometry. Two proteins of interest, microsomal triglyceride transfer protein (MTTP) and sterol regulatory element binding protein 1(SREBP-1), the levels of which were significantly changed in the TNBG-treated cells, were further characterized by western blot assay. A total of 155 proteins, including 56 cytoplasm proteins, 65 membrane proteins and 34 nucleus proteins, were detected to be differentially expressed, and 33 proteins were successfully identified, of which 11 proteins were related to lipid synthesis, 4 proteins to lipid degradation and 3 proteins to lipid transport. Results from Western Blot assay were consistent with proteome analysis. The antitumor effects of TNBG may be related to its interference with lipid metabolism of cancer cells, resulting in accumulation of LDs. MTTP may be a main cause of TNBG induced accumulationof LDs.
关键词：Tetrazanbigen; antitumor; subcellular proteomics; lipid metabolism; microsomal triglyceride transfer protein
