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脱氢枞胺衍生物DHAA-urea对人肝癌HepG2细胞糖代谢的抑制作用

Inhibition of glucometabolism by a novel dehydroabielylamine derivative, DHAA-urea,in human hepatoma HepG2 cells

  • 摘要: 探讨脱氢枞胺衍生物DHAA-urea对有氧和乏氧状态的HepG2细胞的生长及糖代谢的影响。150 μmol/L浓度氯化钴的无血清DMEM预培养24 h致乏氧细胞模型,使用MTT法检测DHAA-urea(1~50 μmol/L)分别对常氧和乏氧HepG2细胞的生长抑制情况。分别使用试剂盒检测DHAA-urea作用常氧与乏氧HepG2后细胞内ATP浓度,乳酸脱氢酶(LDH)以及葡萄糖-6-磷酸脱氢酶(G6PD)活性的变化。与正常对照组比较,DHAA-urea对常氧乏氧HepG2细胞的生长都具有明显的抑制作用,胞内ATP,LDH和G6PD含量与活性均受到抑制,且与DHAA-urea剂量和作用时间呈依赖性。DHAA-urea对HepG2细胞的生长抑制很可能与其抑制糖代谢导致能量耗竭相关。DHAA-urea是抗肿瘤领域较具发展潜力的新化合物。

     

    Abstract: The effects of DHAA-urea,a novel dehydroabietylamine(DHAA) derivatives,on cell viability and glucose metabolism,in hypoxia and normoxia human hepatoma HepG2 cells were investigated.Hypoxia cells were achieved using DMEM containing high concentration of glucose without serum and pre-incubating of CoCl2(final concentration 150 μmol/L) for 24 h.The antiproliferation effect of DHAA.-urea was measured by colorimetric MTT assay.The cellular ATP concentration,the lactate dehydrogenase(LDH) and glucose-6-phosphate dehydrogenase(G6PD)activity were detected by their kits.It was shown that DHAA-urea markedly inhibited cell viability,cellular ATP level,LDH and G6PD activity in either aerobic or anaerobic circumstance in a dose- and time-dependent manner.This suggested that DHAA.-urea possibly inhibited HepG2 cells growth via the inhibition of glucolysis and glucolysis-dependent ATP depletion.DHAA-urea could be a promising candidate in the development of a novel class of agents used for human hepatocellular carcinoma.

     

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