Summary
Tetrazanbigen (TNBG) is a novel synthetic antitumor drug with significant antitumor effects on common solid tumors in vitro and in vivo. It may lead to death of cancer cells through a tumor-associated lipoidosis mechanism, and result in lipid droplets (LDs) accumulation at the cytoplasm. In this study, the effects of TNBG on protein expression in human hepatocellular carcinoma cell line QGY-7701 were studied for elucidating its antitumor mechanism. The proteins extracted from TNBG-treated human hepatocellular carcinoma cell line QGY-7701 were analyzed and compared with control cells by two-dimensional gel electrophoresis. The differential proteins were identified by matrix-associated laser desorption ionization time-of-flight mass (MALDI-TOF-MS) spectrometry. Two proteins of interest, the levels of which were significantly increased in TNBG-treated cells, were further characterized by Western blot analysis. The results showed a total of 846±23 spots in control cells and 853±30 spots in TNBG-treated cells. Twenty-six up-regulated or down-regulated proteins were found by analyzing differential proteomic 2-DE map. Eleven of them were identified by mass spectrometry. They were protein disulfide-isomerase precursor, 94 kD glucose-regulated protein, heat shock protein (HSP) 90-alpha, ATP-citrate lyase, HMG-CoA reductase, glucose-6-phosphate 1-dehydrogenase, very-long-chain specific acyl-CoA dehydrogenase, squalene synthetase, sterol regulatory element-binding protein 1, fructose-bisphosphate aldolase A, and peroxiredoxin-1. These up-regulated or down-regulated proteins are mostly related to lipid metabolism. The TNBG antitumor mechanism is probably to influence tumor lipid metabolism, resulting in accumulation of LDs in tumor cells.
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This project was supported by grants from National Natural Sciences Foundation of China (No. 30772595, No. 3037163 2 and No. 30171070), National Foundation for New Drug Research and Development of China (No. 96-501-5-6), and Chongqing Municipal Sciences Technology Commission (Yu Ke Fa 20021425).
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Yuan, Y., Li, W., Li, L. et al. Effects of tetrazanbigen on the protein expression in human hepatocellular carcinoma cell line QGY-7701. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 304–308 (2009). https://doi.org/10.1007/s11596-009-0308-9
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DOI: https://doi.org/10.1007/s11596-009-0308-9