Li Yang, Luo Qing-ying, Deng Jian-jun, Zhang Zun-zhen
Sichuan Da Xue Xue Bao Yi Xue Ban. 2015 Mar;46(2):163-8.
To study the effect and mechanism of 4-amino-1, 8-naphthalimide (4-AN) on the sensitive effect of arsenic trioxide (ATO) in hepatocellular carcinoma cells.
Hepatocellular carcinoma HepG2 cells were divided into two groups according to whether they were treated with 4-AN or not. Cell viability was evaluated by MTT assay, population doubling experiment and colony formation assay; genic mechanism was explored by 8-OH-dG assay, single cell gel electrophoresis (comet assay) and microriucleus test.
At 2-10 micromol/L concentration of ATO, the cell viability and colony formation efficiency of the combinatio group (4-AN+ATO) were significantly lower than that of the ATO group (P<0.05); moreover, the tail-length (L-Tail) and olive tail moment (OTM) in comet assay were notablely higher than that of the ATO group (P<0.05). At 2-20 micromol/L concentration of ATO, the population doubling time and 8-OH-dG in combination group were significantly higher than that of ATO group (P<0.05). Results from DNA damage repair assay showed that the efficiency of DNA damage repair in combination group was remarkably lower than that of ATO group (P<0.05). At 5-20 micromol/L concentration of ATO, the frequency of micronucleated cells in combination group was significantly higher than that of ATO group (P<0.05).
4-AN can significantly increase the sensitivity of ATO in treatment with hepatocellular carcinoma cells and prevent DNA damage repair may be a primary mechanism for this effect.
研究4-氨基-1,8-萘二甲酰亚胺(4-AN)对三氧化二砷(ATO)在肝癌细胞中敏感作用的影响及机制。
肝癌HepG2细胞根据是否用4-AN处理分为两组。通过MTT法、群体倍增实验和集落形成实验评估细胞活力;通过8-羟基脱氧鸟苷(8-OH-dG)检测、单细胞凝胶电泳(彗星实验)和微核试验探索基因机制。
在2-10μmol/L浓度的ATO作用下,联合组(4-AN+ATO)的细胞活力和集落形成效率显著低于ATO组(P<0.05);此外,彗星实验中的尾长(L-Tail)和橄榄尾矩(OTM)显著高于ATO组(P<0.05)。在2-20μmol/L浓度的ATO作用下,联合组的群体倍增时间和8-OH-dG显著高于ATO组(P<0.05)。DNA损伤修复实验结果显示,联合组的DNA损伤修复效率显著低于ATO组(P<0.05)。在5-20μmol/L浓度的ATO作用下,联合组的微核细胞频率显著高于ATO组(P<0.05)。
4-AN可显著提高ATO对肝癌细胞的治疗敏感性,而阻止DNA损伤修复可能是其产生这种作用的主要机制。