Tabor E, Kim C M
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Med Virol. 1991 May;34(1):45-50. doi: 10.1002/jmv.1890340108.
Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.
评估了在培养基中加入甲磺酸去铁胺（去铁胺，DFX）对人肝癌细胞系（PLC/PRF/5和Hep3B）或肝母细胞瘤细胞系（Hep G2）的抑制作用。当PLC/PRF/5细胞在30或60微摩尔DFX中培养7天时，细胞数量减少30 - 60%，很少或不产生甲胎蛋白（AFP），乙肝表面抗原（HBsAg）的上清终点稀释滴度降低1 - 2个对数。未添加DFX培养7天的PLC/PRF/5细胞（同步对照）生长至汇合，产生的AFP在培养液中达到10 - 60纳克/毫升，且HBsAg滴度保持不变或升高1个对数。与未添加DFX培养的同步对照细胞相比，在DFX中培养的Hep3B和Hep G2细胞也观察到类似效应（除Hep G2细胞不产生HBsAg外）。人胚肺成纤维细胞系（Wl 38）的生长未被DFX显著抑制，尽管其生长速度比未添加DFX培养的同步对照细胞慢。先前在DFX中培养的PLC/PRF/5、Hep3B和Hep G2细胞随后在硫酸亚铁中培养，并未逆转DFX的作用。当PLC/PRF/5细胞在含有等摩尔浓度DFX和氯化铁的培养基以及含有等摩尔浓度DFX和硫酸亚铁的培养基中培养时，也受到抑制。在高达60微摩尔的另一种对铁具有相似亲和力的螯合剂——乙二胺四乙酸二钠钙（EDTA）中培养时，PLC/PRF/5细胞未受到抑制。这些研究表明，无论是否存在整合的乙肝病毒DNA（PLC/PRF/5、Hep3B存在，Hep G2不存在），DFX均能抑制人肝癌细胞系和肝母细胞瘤细胞系的生长。研究结果还表明，这种抑制作用可能是由铁螯合以外的机制引起的。
